JPWO2007094413A1 - Pharmaceutical composition for transdermal administration - Google Patents
Pharmaceutical composition for transdermal administration Download PDFInfo
- Publication number
- JPWO2007094413A1 JPWO2007094413A1 JP2008500544A JP2008500544A JPWO2007094413A1 JP WO2007094413 A1 JPWO2007094413 A1 JP WO2007094413A1 JP 2008500544 A JP2008500544 A JP 2008500544A JP 2008500544 A JP2008500544 A JP 2008500544A JP WO2007094413 A1 JPWO2007094413 A1 JP WO2007094413A1
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- transdermal administration
- water
- skin
- gellan gum
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 113
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 104
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- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
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- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- VIZXMHCBZLGUET-UHFFFAOYSA-N sodium gualenate Chemical compound CC(C)C1=CC=C(C)C2=C(S(O)(=O)=O)C=C(C)C2=C1 VIZXMHCBZLGUET-UHFFFAOYSA-N 0.000 description 1
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- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
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- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本発明の目的は、使用感が良好であり、褥瘡等の皮膚潰瘍の治療効果に優れた経皮投与用医薬組成物を提供することである。(i)次亜塩素酸水、及び(ii)ネイティブ型ジェランガムを組み合わせて、ヒドロゲル状の組成物を調製し、これを経皮投与用医薬組成物として使用する。An object of the present invention is to provide a pharmaceutical composition for transdermal administration which has a good feeling of use and has an excellent therapeutic effect on skin ulcers such as pressure ulcers. A hydrogel composition is prepared by combining (i) hypochlorous acid water and (ii) native gellan gum, and this is used as a pharmaceutical composition for transdermal administration.
Description
本発明は、次亜塩素酸水を含む経皮投与用医薬組成物に関する。より詳細には、褥瘡（床ずれ）等の皮膚潰瘍の治療剤として好適に使用される経皮投与用医薬組成物に関する。更に、本発明は、経皮投与用の医療シート、経皮投与用医薬組成物の製造用キット等に関する。 The present invention relates to a pharmaceutical composition for transdermal administration containing hypochlorous acid water. More specifically, the present invention relates to a pharmaceutical composition for transdermal administration which is suitably used as a therapeutic agent for skin ulcers such as pressure sores (bed sores). Furthermore, the present invention relates to a medical sheet for transdermal administration, a kit for producing a pharmaceutical composition for transdermal administration, and the like.
皮膚潰瘍とは、褥瘡、熱傷、外傷、血行不良、糖尿病等によって皮膚が欠損する皮膚疾患である。皮膚潰瘍の中でも、褥瘡（所謂床ずれ）は、健康状態が悪く長期間臥床する高齢者に多く見られる皮膚潰瘍であり、難治性であることが知られている。従来、褥瘡等の皮膚潰瘍の治療は、一般的には、皮膚潰瘍部位に薬剤を適用した後に、被膜材を用いて当該部位を覆って保護することによって行われている。この従来の治療方法では、皮膚潰瘍部位への薬剤の適用は、薬剤を染み込ませたガーゼで塗布する方法や、薬剤を染み込ませたガーゼを皮膚潰瘍部位に接触させた状態で一定時間固定する方法が採用されている。しかしながら、前者の方法では、皮膚潰瘍部位への薬剤の塗布量が不十分になったり、不均一になるという欠点があり、また後者の方法では、時間と労力を必要とし、更に使用感が悪く患者の負担も大きくなるという欠点がある。 Skin ulcers are skin diseases in which the skin is lost due to pressure ulcers, burns, trauma, poor circulation, diabetes, and the like. Among skin ulcers, pressure ulcers (so-called bed sores) are skin ulcers that are common in elderly people who have poor health and are bedridden for a long time, and are known to be refractory. Conventionally, treatment of skin ulcers such as pressure ulcers is generally performed by applying a drug to the skin ulcer site and then covering and protecting the site with a coating material. In this conventional treatment method, the drug is applied to the skin ulcer site by applying the gauze soaked with the drug or by fixing the gauze soaked with the drug for a certain period of time in contact with the skin ulcer site. Is adopted. However, the former method has the disadvantage that the amount of the drug applied to the skin ulcer site becomes insufficient or non-uniform, and the latter method requires time and labor, and is uncomfortable. There is a disadvantage that the burden on the patient is also increased.
そこで近年、上記欠点が解消された皮膚潰瘍の治療剤として、薬剤を含浸させたヒドロゲル組成物が提案されている。このようなヒドロゲル組成物を使用すると、皮膚潰瘍部位に貼るだけで薬剤の作用を有効に発現させ得るので、非常に簡便に皮膚潰瘍の治療が可能になり、患者の負担も著しく軽減することが期待される。このような薬剤を含浸させたヒドロゲル組成物に関して、種々報告されている。例えば、ゼラチン、糖類及びヨードホルムを含む褥瘡・皮膚潰瘍治療用製剤（特許文献１）；非還元糖、ポビドンヨード、プルラン等を含む褥瘡・皮膚潰瘍治療組成物（特許文献２）；タマリンド種子ガム及びスルファジアジン銀を含む褥瘡用貼付剤（特許文献３）；糖、ポビドンヨード、及びアルギン酸塩を含む褥瘡・損傷皮膚修復用製剤（特許文献４）等が知られている。しかしながら、上記特許文献１−４で使用されているゲル化剤を使用して得られるヒドロゲル組成物では、弾力性、透明性、粘着性等の点を全て満足させることはできず、皮膚に適用した際に使用感が悪いという欠点があった。 Therefore, in recent years, hydrogel compositions impregnated with drugs have been proposed as therapeutic agents for skin ulcers in which the above drawbacks have been eliminated. When such a hydrogel composition is used, the action of the drug can be effectively expressed simply by applying it to the skin ulcer site, so that it is possible to treat skin ulcer very easily and the burden on the patient can be significantly reduced. Be expected. Various reports have been made regarding hydrogel compositions impregnated with such agents. For example, a preparation for treating pressure ulcer / skin ulcer containing gelatin, saccharide and iodoform (Patent Document 1); a composition for treating pressure ulcer / skin ulcer containing non-reducing sugar, povidone iodine, pullulan, etc. (Patent Document 2); tamarind seed gum and sulfadiazine Known pressure ulcer patches containing silver (Patent Document 3); pressure ulcer / damaged skin repair formulations (Patent Document 4) containing sugar, povidone iodine, and alginates are known. However, the hydrogel composition obtained by using the gelling agent used in Patent Documents 1-4 cannot satisfy all the points such as elasticity, transparency and adhesiveness, and is applied to the skin. When used, there was a disadvantage that the feeling of use was bad.
また、皮膚潰瘍の治療に使用される薬剤としては、次亜塩素酸水やポビドンヨード等の消毒剤を含むものが有効であると考えられている。しかしながら、皮膚潰瘍の治療に使用される消毒剤の内、ポビドンヨードについては、有色であるが故に、皮膚に適用すると不可避的に皮膚を着色してしまうという欠点がある。ポビドンヨードによる皮膚の着色は洗浄しても落ち難いため、ポビドンヨードを含むヒドロゲル組成物については、使用者にとって心理的忌避感がある。一方、皮膚潰瘍の治療に使用される消毒剤として、次亜塩素酸水については、無色透明であってポビドンヨードのような皮膚の着色化という問題点がなく、皮膚潰瘍の治療効果も優れていることが分かっている。しかしながら、次亜塩素酸水は熱に対して不安定であり、高温下では塩素が揮散するという欠点がある。ヒドロゲル組成物の調製においてゲル化剤の加熱溶解は不可欠であるため、上記特許文献１−４で使用されているゲル化剤と共に次亜塩素酸水を配合してゲル組成物を調製しても、塩素が揮散してゲル組成物中の次亜塩素酸が損なわれてしまうことが分かっている。また、予めヒドロゲルを調製した後に水分を揮散させて乾燥ゲルにし、この乾燥ゲルに薬液を含浸させる方法によって、薬液を高温に晒すことなく薬液含有ヒドロゲル組成物を調製し得ることが分かっている。しかしながら、次亜塩素酸水は、従来医薬用途に使用されていたゲル化剤で調製された乾燥ゲルに対しては、吸収され難いという性質があり、かかる方法によっても、従来医薬用途に使用されていたゲル化剤の使用では、次亜塩素酸水を十分に含有させることは困難である。 Moreover, it is thought that what contains disinfectants, such as hypochlorous acid water and povidone iodine, is effective as a medicine used for the treatment of skin ulcer. However, among disinfectants used for the treatment of skin ulcers, povidone iodine is colored, and therefore has the disadvantage that it inevitably colors the skin when applied to the skin. Since the skin coloration by povidone iodine is difficult to remove even after washing, the hydrogel composition containing povidone iodine has a psychological avoidance to the user. On the other hand, as a disinfectant used for the treatment of skin ulcer, hypochlorous acid water is colorless and transparent, has no problem of coloring the skin like povidone iodine, and has an excellent therapeutic effect on skin ulcer. I know that. However, hypochlorous acid water is unstable with respect to heat, and has a drawback that chlorine is volatilized at a high temperature. In the preparation of the hydrogel composition, heating and dissolution of the gelling agent is indispensable, so even if the gel composition is prepared by blending hypochlorous acid water together with the gelling agent used in Patent Documents 1-4 above. It is known that chlorine is volatilized and hypochlorous acid in the gel composition is damaged. Moreover, it has been found that a chemical solution-containing hydrogel composition can be prepared without exposing the chemical solution to a high temperature by a method in which water is volatilized into a dry gel after the hydrogel is prepared in advance and the dry gel is impregnated with the chemical solution. However, hypochlorous acid water has a property that it is difficult to be absorbed by a dry gel prepared with a gelling agent that has been conventionally used for pharmaceutical use, and such a method is also conventionally used for pharmaceutical use. It is difficult to sufficiently contain hypochlorous acid water by using the former gelling agent.
一方、これまでに、次亜塩素酸水を含むヒドロゲル組成物の具体的処方については報告されていない。また、次亜塩素酸水及びネイティブ型ジェランガムを含有するヒドロゲル組成物が、皮膚潰瘍の治療において如何なる効果を奏し得るかについても明らかにされていない。
本発明は上記の実情に鑑みてなされたものであり、使用感が良好であり、褥瘡等の皮膚潰瘍の治療効果に優れた経皮投与用医薬組成物及び医療シートを提供することを目的とする。 The present invention has been made in view of the above circumstances, and has an object to provide a pharmaceutical composition and a medical sheet for transdermal administration which have a good feeling of use and are excellent in the effect of treating skin ulcers such as pressure ulcers. To do.
本発明者らは、上記課題を解決すべく鋭意研究を重ねていたところ、次亜塩素酸水を含み、且つネイティブ型ジェランガムを必須ゲル化剤として含有するヒドロゲル状の組成物が、非常に弾力に富み、患部への付着性も高く、更には脱着時の剥離性にも優れるゲルとなり、従来品より経皮投与用医薬組成物として好ましい物性が付与されることを見いだした。また、ネイティブ型ジェランガムに加えて脱アシル型ジェランガムと併用して使用すると、ヒドロゲル組成物の硬さや強度を強化することができることを見いだした。更に、当該経皮投与用医薬組成物において、ネイティブ型ジェランガムと次亜塩素酸水を組み合わせて含有することにより、皮膚潰瘍の治療効果が顕著に高められていることを見いだした。本発明は、これらの知見に基づいて更に改良を重ねることにより完成したものである。 The inventors of the present invention have made extensive studies in order to solve the above-mentioned problems. As a result, a hydrogel composition containing hypochlorous acid water and containing native gellan gum as an essential gelling agent is very elastic. It was found to be a gel that is rich in, highly adherent to the affected area, and excellent in releasability at the time of desorption, and is given a preferable physical property as a pharmaceutical composition for transdermal administration than the conventional product. Further, it has been found that the hardness and strength of the hydrogel composition can be enhanced when used in combination with deacylated gellan gum in addition to native gellan gum. Furthermore, it has been found that the therapeutic effect of skin ulcer is remarkably enhanced by containing a combination of native gellan gum and hypochlorous acid water in the pharmaceutical composition for transdermal administration. The present invention has been completed by making further improvements based on these findings.
即ち、本発明は、下記の経皮投与用医薬組成物を提供する：
項１． (i)次亜塩素酸水、及び(ii)ネイティブ型ジェランガムを含有し、ヒドロゲルの形態であることを特徴とする、経皮投与用医薬組成物。
項２． 更に(iii)脱アシル型ジェランガムを含有する、項１に記載の経皮投与用医薬組成物。
項３． シート状である、項１に記載の経皮投与用医薬組成物。
項４． 皮膚潰瘍治療剤である、項１に記載の経皮投与用医薬組成物。
項５． 褥瘡治療剤である、項１に記載の経皮投与用医薬組成物。That is, the present invention provides the following pharmaceutical composition for transdermal administration:
Item 1. A pharmaceutical composition for transdermal administration, comprising (i) hypochlorous acid water and (ii) native gellan gum and in the form of a hydrogel.
Item 2. Item 2. The pharmaceutical composition for transdermal administration according to Item 1, further comprising (iii) deacylated gellan gum.
Item 3. Item 2. The pharmaceutical composition for transdermal administration according to Item 1, which is in a sheet form.
Item 4. Item 2. The pharmaceutical composition for transdermal administration according to Item 1, which is a skin ulcer therapeutic agent.
Item 5. Item 2. The pharmaceutical composition for transdermal administration according to Item 1, which is a therapeutic agent for pressure ulcer.
また、本発明は、下記の経皮投与用の医療シートを提供する：
項６． 吸水性素材からなり皮膚に貼付される吸水層と、該吸水層上に項３に記載の経皮投与用医薬組成物が積層されてなる、経皮投与用の医療シート。
項７． 前記吸水層が次亜塩素酸水を含むものである、項６に記載の経皮投与用の医療シート。
項８． 前記経皮投与用医薬組成物が、更に(iii)脱アシル型ジェランガムを含有するものである、項６に記載の医療シート。
項９． 皮膚潰瘍治療用である、項６に記載の医療シート。
項１０． 褥瘡治療用である、項６に記載の医療シート。The present invention also provides the following medical sheet for transdermal administration:
Item 6. A medical sheet for transdermal administration, comprising a water-absorbing layer made of a water-absorbing material, and a pharmaceutical composition for transdermal administration according to Item 3 laminated on the water-absorbing layer.
Item 7. Item 7. The medical sheet for transdermal administration according to Item 6, wherein the water-absorbing layer contains hypochlorous acid water.
Item 8. Item 7. The medical sheet according to Item 6, wherein the pharmaceutical composition for transdermal administration further comprises (iii) deacylated gellan gum.
Item 9. Item 7. The medical sheet according to Item 6, which is used for treating skin ulcer.
Item 10. Item 7. The medical sheet according to Item 6, which is used for treating pressure ulcers.
更に、本発明は、下記の経皮投与用医薬組成物の製造用キットを提供する：
項１１． (a)次亜塩素酸水を含有する薬液、及び(b)ネイティブ型ジェランガムを含有するヒドロゲルを乾燥してなる乾燥ゲルを含有することを特徴とする、経皮投与用医薬組成物の製造用キット。
項１２． 乾燥ゲルがネイティブ型ジェランガム及び脱アシル型ジェランガムを含有するヒドロゲルを乾燥してなるものである、項１１に記載のキット。
項１３． 経皮投与用医薬組成物がシート状である、項１１に記載のキット。
項１４． 経皮投与用医薬組成物が、皮膚潰瘍治療剤である、項１１に記載のキット。
項１５． 経皮投与用医薬組成物が、褥瘡治療剤である、項１１に記載のキット。Furthermore, the present invention provides the following kit for producing a pharmaceutical composition for transdermal administration:
Item 11. For producing a pharmaceutical composition for transdermal administration, comprising: (a) a chemical solution containing hypochlorous acid water; and (b) a dried gel obtained by drying a hydrogel containing native gellan gum. kit.
Item 12. Item 12. The kit according to Item 11, wherein the dried gel is obtained by drying a hydrogel containing native gellan gum and deacylated gellan gum.
Item 13. Item 12. The kit according to Item 11, wherein the pharmaceutical composition for transdermal administration is in sheet form.
Item 14. Item 12. The kit according to Item 11, wherein the pharmaceutical composition for transdermal administration is a therapeutic agent for skin ulcer.
Item 15. Item 12. The kit according to Item 11, wherein the pharmaceutical composition for transdermal administration is a therapeutic agent for pressure ulcer.
更に、本発明は、下記治療方法及び使用を提供する。
項１６． 皮膚潰瘍を患っている患者の皮膚潰瘍患部に、項１に記載の経皮投与用医薬組成物、又は項６に記載の医療シートを適用することを特徴とする、皮膚潰瘍の治療方法。
項１７． 項１に記載の経皮投与用医薬組成物の、皮膚潰瘍治療剤の製造のための使用。
項１８． 項６に記載の医療シートの、皮膚潰瘍治療剤の製造のための使用。Furthermore, the present invention provides the following treatment methods and uses.
Item 16. Item 7. A method for treating skin ulcer, comprising applying the pharmaceutical composition for transdermal administration according to Item 1 or the medical sheet according to Item 6 to a skin ulcer affected part of a patient suffering from skin ulcer.
Item 17. Item 8. Use of the pharmaceutical composition for transdermal administration according to Item 1 for producing a skin ulcer therapeutic agent.
Item 18. Item 7. Use of the medical sheet according to Item 6 for producing a skin ulcer therapeutic agent.
本発明の経皮投与用医薬組成物によれば、(i)次亜塩素酸水及び(ii)ネイティブ型ジェランガムを組み合わせて含有し、ヒドロゲルの形態であることにより、弾力に富む、患部への付着性も高い、脱着時の剥離性が容易である等の優れた効果を示し、良好な使用感を得ることができる。また、(i)次亜塩素酸水及び(ii)ネイティブ型ジェランガムを併用することによって、皮膚潰瘍、特に褥瘡に対する治療効果を一層増強して奏することができる。このように、本発明の経皮投与用医薬組成物は、使用感及び治療効果が共に優れており、皮膚潰瘍治療剤として有用性が高い。 According to the pharmaceutical composition for transdermal administration of the present invention, it contains (i) hypochlorous acid water and (ii) native gellan gum in combination, and is in the form of a hydrogel. Excellent effects such as high adhesion and easy releasability at the time of desorption are obtained, and a good feeling of use can be obtained. In addition, the combined use of (i) hypochlorous acid water and (ii) native gellan gum can further enhance the therapeutic effect on skin ulcers, particularly pressure ulcers. As described above, the pharmaceutical composition for transdermal administration of the present invention has both excellent usability and therapeutic effect, and is highly useful as a skin ulcer therapeutic agent.
更に、本発明の経皮投与用医薬組成物は、(a)可食ゲル化剤を使用していることに基づいて安全性が高い、(b)保水性や保水安定性効果（離水抑制）を有する、(c)熱安定性に優れている、(d)凍結解凍前後においてヒドロゲルの物性が変化しない、等といった優れた特性をも有しており、有用性が高い。これに加えて、本発明の経皮投与用医薬組成物は、該組成物自体に透明性をも備えることができるので、皮膚患部に貼付した状態であっても、患部の症状をモニタリングできるという利点が得られる。 Furthermore, the pharmaceutical composition for transdermal administration of the present invention has (a) high safety based on the use of an edible gelling agent, (b) water retention and water retention stability effect (water separation inhibition) (C) excellent thermal stability, (d) the physical properties of the hydrogel do not change before and after freezing and thawing, and the like. In addition, since the pharmaceutical composition for transdermal administration of the present invention can also have transparency in the composition itself, it can monitor the symptoms of the affected area even when it is attached to the affected area of the skin. Benefits are gained.
更に、本発明の経皮投与用の医療シートは、上記経皮投与用医薬組成物による皮膚潰瘍の治療効果を一層有効に奏させることができるので、臨床上の有用性が極めて高い。 Furthermore, since the medical sheet for transdermal administration of the present invention can exhibit the effect of treating skin ulcers more effectively with the pharmaceutical composition for transdermal administration, it has extremely high clinical usefulness.
１．経皮投与用医薬組成物
本発明の経皮投与用医薬組成物は、ヒドロゲル（含水ゲル）の形態であり、特定の薬剤及び特定のゲル化剤を含むことを特徴とするものである。 1. Pharmaceutical composition for transdermal administration The pharmaceutical composition for transdermal administration of the present invention is in the form of a hydrogel (hydrous gel) and contains a specific drug and a specific gelling agent.
本発明の医薬組成物は、薬剤として(i)次亜塩素酸水を含有する。次亜塩素酸水は、酸性電解水とも呼ばれ、次亜塩素酸を含有する水溶液であり、消毒剤として公知である。本発明で使用される次亜塩素酸水は、その有効塩素濃度は、皮膚潰瘍の治療効果が奏される限り特に制限されないが、通常１〜５００ｐｐｍ、好ましくは５〜１００ｐｐｍ、更に好ましくは１０〜５０ｐｐｍが例示される。なお、本発明において、次亜塩素酸水は、公知の次亜塩素酸水の製造方法で直接的に得られたものを使用することができるが、上記範囲よりも高い有効塩素濃度の次亜塩素酸水に対して水を適量混合することによって得られたものを使用してもよい。 The pharmaceutical composition of the present invention contains (i) hypochlorous acid water as a drug. Hypochlorous acid water is also called acidic electrolyzed water, is an aqueous solution containing hypochlorous acid, and is known as a disinfectant. The effective concentration of hypochlorous acid used in the present invention is not particularly limited as long as the therapeutic effect on skin ulcer is exhibited, but is usually 1 to 500 ppm, preferably 5 to 100 ppm, and more preferably 10 to 10 ppm. 50 ppm is exemplified. In the present invention, as the hypochlorous acid water, those obtained directly by a known method for producing hypochlorous acid water can be used, but hypochlorous acid having an effective chlorine concentration higher than the above range can be used. You may use what was obtained by mixing a proper quantity of water with chloric acid water.
また、本発明で使用される次亜塩素酸水のｐＨとしては、特に制限されるものではない。例えば、強酸性の次亜塩素酸水であってもよく、また弱酸性の次亜塩素酸水であってもよい。強酸性の次亜塩素酸水の場合であれば、そのｐＨとしては、好ましくは２〜３、更に好ましくは２．２〜２．８が挙げられる。また、弱酸性の次亜塩素酸水の場合であれば、そのｐＨとしては、好ましくは５〜７．５、更に好ましくは５〜６．５が挙げられる。中でも、好ましくは強酸性の次亜塩素酸水であり、このようなｐＨの次亜塩素酸水を使用することにより、褥瘡を初めとする皮膚潰瘍の治療効果を一層有効に発現させることが可能になる。 Moreover, it does not restrict | limit especially as pH of the hypochlorous acid water used by this invention. For example, it may be strongly acidic hypochlorous acid water or weakly acidic hypochlorous acid water. In the case of strongly acidic hypochlorous acid water, the pH is preferably 2 to 3, more preferably 2.2 to 2.8. In the case of weakly acidic hypochlorous acid water, the pH is preferably 5 to 7.5, more preferably 5 to 6.5. Among them, strong acidic hypochlorous acid water is preferable, and by using hypochlorous acid water having such a pH, the therapeutic effect of skin ulcers such as pressure ulcers can be expressed more effectively. become.
本発明の医薬組成物において、次亜塩素酸水の含有割合については、特に制限されないが、例えば、該医薬組成物の総量に対して、５〜９９重量％、好ましくは２０〜９８重量％、更に好ましくは５０〜９５重量％が例示される。なお、ここで、次亜塩素酸水の含有割合とは、医薬組成物（ヒドロゲル組成物）に含まれるゲル化剤、次亜塩素酸水及び必要に応じて添加する他の成分を加えた医薬組成物全量に対する次亜塩素酸水の含有割合を意味する。 In the pharmaceutical composition of the present invention, the content of hypochlorous acid water is not particularly limited, but for example, 5 to 99% by weight, preferably 20 to 98% by weight, based on the total amount of the pharmaceutical composition, More preferably, it is 50 to 95% by weight. In addition, the content rate of hypochlorous acid water here is the pharmaceutical which added the gelling agent contained in a pharmaceutical composition (hydrogel composition), hypochlorous acid water, and the other component added as needed. It means the content ratio of hypochlorous acid water relative to the total amount of the composition.
また、本発明の医薬組成物は、ゲル化剤として、(ii)ネイティブ型ジェランガムを必須成分として含有する。本来、ヒドロゲル形態の組成物に使用可能なゲル化剤としては、さまざまな素材が存在するが、本発明では、多数存在するゲル化剤の中でも、(ii)ネイティブ型ジェランガムを選択し、これを上記(i)次亜塩素酸水と組み合わせて使用することを必須とする。ネイティブ型ジェランガムは、食品添加物としてゼリーなどの加工食品において使用実績のある糖類であり、安全性が高いことが既に実証されている。 The pharmaceutical composition of the present invention contains (ii) native gellan gum as an essential component as a gelling agent. Originally, there are various materials as a gelling agent that can be used in a composition in a hydrogel form.In the present invention, among many existing gelling agents, (ii) native gellan gum is selected and used. It is essential to use in combination with the above (i) hypochlorous acid water. Native gellan gum is a saccharide that has been used in processed foods such as jelly as a food additive, and has already been demonstrated to have high safety.
ジェランガムは水生植物の表面から分離された非病原性微生物であるシュードモナス・エロデア（Pseudomonas elodea: ATCC31461）又はその同等株を用いて産生される多糖類であり、脱アシル型ジェランガムは、1-3結合したグルコース、1-4結合したグルクロン酸、1-4結合したグルコースおよび1-4結合したラムノースの４分子の糖を構成単位とする直鎖状の高分子多糖類である。１構成単位当たり、カルボキシル基１残基を有する。ネイティブ型ジェランガムは、1-3結合したグルコース残基に１構成単位当たりグリセリル基１残基とアセチル基が平均１／２残基結合したものであり、脱アシル型ジェランガム（特開昭５５−７９３９７号公報）の脱アシル処理前の前駆体として得られる微生物起源の高分子多糖類である。Gellan gum is a polysaccharide produced using Pseudomonas elodea (ATCC31461) or its equivalent, a non-pathogenic microorganism isolated from the surface of aquatic plants. It is a linear high-molecular-weight polysaccharide comprising four sugar molecules: glucose, 1-4 linked glucuronic acid, 1-4 linked glucose and 1-4 linked rhamnose. One structural unit has one carboxyl group residue. Native gellan gum is obtained by bonding one residue of glyceryl group and one half of acetyl group on average to one to three bonded glucose residues, and deacylated gellan gum (Japanese Patent Laid-Open No. 55-79397). No.) is a high-molecular-weight polysaccharide derived from microorganisms obtained as a precursor before the deacylation process.
ネイティブ型ジェランガムを用いてヒドロゲル形態にした医薬組成物は、非常に弾力に富み、脱着時の患部への付着性や剥離性にも優れるため、皮膚潰瘍治療剤として非常に有効であると考えられる。 A pharmaceutical composition in the form of a hydrogel using native gellan gum is very elastic and has excellent adhesion and exfoliation to the affected area at the time of desorption, so it is considered to be very effective as a therapeutic agent for skin ulcer .
ネイティブ型ジェランガムの配合割合は、本発明の医薬組成物に求められる硬さや強度等に応じて適宜設定されるが、その一例として、該医薬組成物の総量に対して、０．５〜１０重量％、好ましくは０．８〜３重量％、更に好ましくは１〜２重量％を挙げることができる。 The blending ratio of the native gellan gum is appropriately set according to the hardness and strength required for the pharmaceutical composition of the present invention. As an example, the blending ratio of 0.5 to 10% by weight with respect to the total amount of the pharmaceutical composition %, Preferably 0.8 to 3% by weight, more preferably 1 to 2% by weight.
本発明の医薬組成物には、ゲル化剤として、上記(ii)ネイティブ型ジェランガムに加えて、(iii)脱アシル型ジェランガムを配合しても良い。脱アシル型ジェランガムを併用することで、医薬組成物の硬さや強度を任意に調整することができる。更に、上記(ii)と(iii)のゲル化剤を併用すれば、本発明の医薬組成物を、良好な物性を備えた薄いシート状にすることが可能になる。このように薄くすることによりシートの軽量化を図ることができるため、コストメリットもある他、医薬組成物を肌などに使用した場合の使用感も向上するという効果がある。 In addition to the above (ii) native gellan gum, (iii) deacylated gellan gum may be added to the pharmaceutical composition of the present invention as a gelling agent. By using deacylated gellan gum in combination, the hardness and strength of the pharmaceutical composition can be arbitrarily adjusted. Furthermore, when the gelling agents (ii) and (iii) are used in combination, the pharmaceutical composition of the present invention can be made into a thin sheet having good physical properties. Since the sheet can be reduced in weight by being made thin in this way, there is an advantage that the merit of using the pharmaceutical composition on the skin is improved in addition to the cost merit.
(ii)ネイティブ型ジェランガムと(iii)脱アシル型ジェランガムを併用する場合、これらの配合比率としては、(ii)ネイティブ型ジェランガム１００重量部に対して、(iii)脱アシル型ジェランガムが、通常１〜５００重量部、好ましくは２〜１００重量部、更に好ましくは５〜５０重量部が例示される。このような比率にすることにより、経皮投与される組成物に求められる適切な柔軟性と強度を兼ね備える医薬組成物とすることができる。ネイティブ型ジェランガムの添加量が多くなると、弾力が強くなる傾向があり、少ないと弾力が減少する。脱アシル型ジェランガムの添加量が多くなると硬くなる傾向があり、少なくなると柔らかくなる傾向がある。 When (ii) native gellan gum and (iii) deacylated gellan gum are used in combination, (iii) 100% by weight of native gellan gum, (iii) deacylated gellan gum is usually 1 -500 weight part, Preferably it is 2-100 weight part, More preferably, 5-50 weight part is illustrated. By setting it as such a ratio, it can be set as the pharmaceutical composition which has the appropriate softness | flexibility and intensity | strength calculated | required by the composition administered percutaneously. When the amount of native gellan gum is increased, the elasticity tends to increase, and when it is less, the elasticity decreases. When the amount of deacylated gellan gum added is increased, it tends to be hard, and when it is decreased, it tends to be soft.
また、(iii)脱アシル型ジェランガムを配合する場合、その配合割合については、上記配合比率を充足するように適宜設定すればよいが、一例として、医薬組成物の総量に対して０．０１〜５重量％、好ましくは０．０５〜１重量％、更に好ましくは０．１〜０．５重量％となる割合が挙げられる。 In addition, when (iii) deacylated gellan gum is blended, the blending ratio may be appropriately set so as to satisfy the blending ratio, but as an example, 0.01 to 0.01 to the total amount of the pharmaceutical composition A proportion of 5% by weight, preferably 0.05 to 1% by weight, and more preferably 0.1 to 0.5% by weight.
本発明の医薬組成物は、必要に応じて、更に、ゲル化剤として、寒天、ガラクトマンナン（ローカストビーンガム、グァーガム、タラガム）、サイリウムシードガム、ゼラチン、カラギナン、キサンタンガム、タマリンドシードガム、プルラン、ペクチン等を１種又は２種以上含んでいても良い。 If necessary, the pharmaceutical composition of the present invention may further contain, as a gelling agent, agar, galactomannan (locust bean gum, guar gum, tara gum), psyllium seed gum, gelatin, carrageenan, xanthan gum, tamarind seed gum, pullulan, 1 type or 2 types or more of pectin etc. may be included.
ゲル化剤として、(iii)脱アシル型ジェランガムを配合する場合、カルシウム塩及び／又は酸化カルシウムを添加することで、より硬いヒドロゲル形態の組成物を調製することができる。このようなカルシウム塩としては、有機酸又は無機酸の水溶性カルシウム塩が挙げられ、より具体的には、乳酸カルシウム、グルコン酸カルシウム、塩化カルシウム、乳清カルシウム、クエン酸カルシウム等の水溶性カルシウム塩が挙げられる。中でも乳酸カルシウムを使用するのが好ましい。カルシウム塩及び／又は酸化カルシウムの配合割合としては、医薬組成物の総量に対して、カルシウム原子の重量換算で、例えば０．０００５〜０．２重量％、好ましくは０．００１〜０．１重量％、更に好ましくは０．００２〜０．０３重量％が例示される。カルシウム塩の配合割合として、より具体的には、乳酸カルシウムを使用する場合であれば、医薬組成物の総量に対して、例えば０．００５〜１重量％、好ましくは０.０１〜０．５重量％、更に好ましくは０．０２〜０．２重量％を挙げることができる。 When (iii) deacylated gellan gum is added as a gelling agent, a harder hydrogel composition can be prepared by adding calcium salt and / or calcium oxide. Examples of such calcium salts include water-soluble calcium salts of organic acids or inorganic acids, and more specifically, water-soluble calcium such as calcium lactate, calcium gluconate, calcium chloride, whey calcium, calcium citrate and the like. Salt. Of these, calcium lactate is preferably used. The blending ratio of the calcium salt and / or calcium oxide is, for example, 0.0005 to 0.2% by weight, preferably 0.001 to 0.1% by weight in terms of calcium atoms based on the total amount of the pharmaceutical composition. %, More preferably 0.002 to 0.03% by weight. More specifically, when calcium lactate is used as a blending ratio of the calcium salt, for example, 0.005 to 1% by weight, preferably 0.01 to 0.5% with respect to the total amount of the pharmaceutical composition. % By weight, more preferably 0.02 to 0.2% by weight.
また、本発明の医薬組成物には、上記成分に加えて、ヒドロゲル組成物の安定化剤として、多価アルコール、糖アルコール、糖類等を含んでいても良い。これの成分として、より具体的には、プロピレングリコール、グリセリン等の多価アルコール；マンニトール、エリスリトール等の糖アルコール；ブドウ糖、果糖等の単糖類；ショ糖、トレハロース等の二糖類；デンプン等の多糖類等の糖類が例示される。これらの安定化剤を配合する場合、これらの安定化剤の配合割合については、通常、医薬組成物の総量に対して、１〜５０重量％となる範囲から適宜選択される。 Moreover, in addition to the said component, the pharmaceutical composition of this invention may contain a polyhydric alcohol, sugar alcohol, saccharides, etc. as a stabilizer of a hydrogel composition. More specifically, the components include polyhydric alcohols such as propylene glycol and glycerin; sugar alcohols such as mannitol and erythritol; monosaccharides such as glucose and fructose; disaccharides such as sucrose and trehalose; Examples include saccharides such as saccharides. When blending these stabilizers, the blending ratio of these stabilizers is usually appropriately selected from a range of 1 to 50% by weight with respect to the total amount of the pharmaceutical composition.
更に、本発明の医薬組成物には、必要に応じて、本発明の効果を妨げないことを限度として、薬学的に許容される各種成分を適宜配合することができる。このような成分としては、例えば、創傷治療剤、局所麻酔剤、抗炎症剤、抗ヒスタミン剤、止血剤、消毒剤、保湿剤、エモリエント剤、殺菌剤、色素、顔料、香料、緩衝剤、ｐＨ調整剤等が挙げられる。これらの成分として、より具体的には、ヒノキチオール、グリチルリチン酸、尿素等の創傷治療剤；塩酸ジブカイン、塩酸プロカイン、ベンゾカイン、リドカイン等の局所麻酔剤；コーチゾン、プレドニゾロン、ベタメサゾン等の抗炎症剤；マレイン酸クロルフェニラミン、塩酸ジフェンヒドラミン、グアイアズレンスルホン酸ナトリウム等の抗ヒスタミン剤；塩酸ナファゾリン、塩酸エフェドリン等の止血剤；アロエ、イクタモール、ポビドンヨード、ヒビデン等の消毒剤；ポリエチレングリコール類、ポリプロピレングリコール類、グリセリン類、単糖類、多糖類等の保湿剤；流動パラフィン、スクワレン、オリーブ油等のエモリエント剤等が例示される。 Furthermore, in the pharmaceutical composition of the present invention, various pharmaceutically acceptable components can be appropriately blended as needed, as long as the effects of the present invention are not hindered. Examples of such components include wound treatment agents, local anesthetics, anti-inflammatory agents, antihistamines, hemostatic agents, disinfectants, moisturizers, emollients, bactericides, dyes, pigments, fragrances, buffers, pH adjusters. Etc. More specifically, as these components, wound treatment agents such as hinokitiol, glycyrrhizic acid and urea; local anesthetics such as dibucaine hydrochloride, procaine hydrochloride, benzocaine and lidocaine; anti-inflammatory agents such as cortisone, prednisolone and betamethasone; Antihistamines such as chlorpheniramine acid, diphenhydramine hydrochloride, sodium guaiazulene sulfonate; hemostatic agents such as naphazoline hydrochloride and ephedrine hydrochloride; disinfectants such as aloe, ictamol, povidone iodine, and hibidene; Examples of humectants such as saccharides and polysaccharides; emollients such as liquid paraffin, squalene and olive oil.
本発明の医薬組成物は、皮膚患部に貼り付けて使用されるので、シート状であることが望ましい。本発明の医薬組成物をシート状にする場合、その厚みについては、適用される皮膚部位に応じて適宜設定されるが、良好な使用感や優れた皮膚潰瘍治療効果を得るには、０．０１〜２０ｍｍ程度にしておくことが望ましい。 Since the pharmaceutical composition of the present invention is used by being affixed to the affected skin area, it is preferably in the form of a sheet. When the pharmaceutical composition of the present invention is formed into a sheet shape, the thickness is appropriately set according to the applied skin site, but in order to obtain a good feeling of use and an excellent skin ulcer treatment effect, the thickness is set to 0. It is desirable to be about 01-20 mm.
本発明の医薬組成物は、後述するように、吸水性素材からなる吸水層を設け、当該吸水層を介して皮膚に適用することができるが、患部に直接適用して使用してもよい。このように皮膚に直接適用しても、本発明の医薬組成物は、使用後の剥離性にも優れ、剥がし残りが生じない点でも有用である。 As will be described later, the pharmaceutical composition of the present invention is provided with a water-absorbing layer made of a water-absorbing material and can be applied to the skin through the water-absorbing layer. As described above, even when directly applied to the skin, the pharmaceutical composition of the present invention is excellent in peelability after use, and is useful in that no peeling residue occurs.
また、本発明の医薬組成物がシート状である場合、該医薬組成物の皮膚非接触面（即ち、皮膚に適用される面とは反対側の面）は、液体不透過性素材及び／又は液体透過性素材からなる支持体を設けることもできる。このような支持体を設けておくことによって、医薬組成物の使用中の乾燥を防止したり、メディカルテープによる患部への固定を容易にすることができ、ひいては治療効果及び取扱性を向上させることが可能になる。当該支持体に使用される液体不透過性素材としては、例えば、レーヨン、ナイロン、アクリル、ポリエチレン、ポリプロピレン等のポリマーからなるシート又はフィルム等が挙げられる。当該支持体に使用される液体透過性素材としては、天然繊維又は合成繊維からなる織布や不織布等が挙げられる。また、当該液体透過性素材として、ガーゼ、脱脂綿等を使用することもできる。当該支持体の厚さも特に制限されず、使い勝手を考慮して適宜選択することができる。また、当該支持体は、皮膚患部に適用する時に当該患部の形状に適合するように伸縮性をある程度有するものが好ましい。更に、当該支持体は、本発明の医薬組成物の形状や患部そのものよりも大きめに設定され、その周縁部に粘着剤が塗布されていることが望ましい。 Further, when the pharmaceutical composition of the present invention is in sheet form, the non-skin contact surface of the pharmaceutical composition (that is, the surface opposite to the surface applied to the skin) is a liquid-impermeable material and / or A support made of a liquid permeable material can also be provided. By providing such a support, drying during use of the pharmaceutical composition can be prevented, and fixation to the affected area with a medical tape can be facilitated, thereby improving the therapeutic effect and handleability. Is possible. Examples of the liquid-impermeable material used for the support include a sheet or film made of a polymer such as rayon, nylon, acrylic, polyethylene, and polypropylene. Examples of the liquid permeable material used for the support include woven fabrics and nonwoven fabrics made of natural fibers or synthetic fibers. Moreover, gauze, absorbent cotton, etc. can also be used as the liquid permeable material. The thickness of the support is not particularly limited, and can be appropriately selected in consideration of convenience. Further, the support preferably has a certain degree of stretchability so as to conform to the shape of the affected part when applied to the affected part of the skin. Furthermore, it is desirable that the support is set to be larger than the shape of the pharmaceutical composition of the present invention and the affected part itself, and an adhesive is applied to the peripheral part thereof.
本発明の医薬組成物は、適用される皮膚及び患部の状態、形状に応じて、適宜形状を調整して、皮膚患部に適用される。 The pharmaceutical composition of the present invention is applied to the affected skin area by appropriately adjusting the shape according to the state and shape of the applied skin and affected area.
本発明の医薬組成物の１回当たりの使用時間については、適用対象皮膚疾患の種類や症状の程度、該医薬組成物の厚みや含有成分の種類、該医薬組成物の適用方法等に応じて適宜設定される。通常、１回当たりの使用時間として３分〜１００時間を挙げることができ、必要に応じて随時新しいものに交換して使用することが望ましい。 About the usage time per time of the pharmaceutical composition of the present invention, it depends on the kind and symptom level of the skin disease to be applied, the thickness of the pharmaceutical composition and the kind of the component, the application method of the pharmaceutical composition, etc. Set as appropriate. Usually, the usage time per time can be 3 minutes to 100 hours, and it is desirable to replace it with a new one as needed.
本発明の医薬組成物は、褥瘡、熱傷、外傷、血行不良、糖尿病による皮膚の欠損等の皮膚潰瘍に対する治療剤として使用できるが、特に難治性の皮膚潰瘍である褥瘡に対する治療効果が優れており、褥瘡治療剤として有用である。 The pharmaceutical composition of the present invention can be used as a therapeutic agent for skin ulcers such as pressure ulcers, burns, trauma, poor blood circulation, skin defects due to diabetes, etc., and is particularly effective for treating pressure ulcers that are intractable skin ulcers. It is useful as a therapeutic agent for pressure ulcers.
本発明の医薬組成物は、所定量の各配合成分を混合して、加温条件下で十分に溶解した後に冷却することにより調製することができるが、好ましくは、(a)次亜塩素酸水を含有する薬液（以下、単に「(a)薬液」と表記することもある）、及び(b)ネイティブ型ジェランガムを含有するヒドロゲルを乾燥してなる乾燥ゲル（以下、単に「(b)乾燥ゲル」と表記することもある）を予め調製しておき、当該(a)薬液を(b)乾燥ゲルに含浸させることにより調製される。 The pharmaceutical composition of the present invention can be prepared by mixing a predetermined amount of each compounding component, sufficiently dissolving under warming conditions, and then cooling, preferably (a) hypochlorous acid A chemical solution containing water (hereinafter sometimes simply referred to as “(a) chemical solution”), and (b) a dry gel obtained by drying a hydrogel containing native gellan gum (hereinafter simply referred to as “(b) dry” (Also referred to as “gel”) is prepared in advance, and (b) a dry gel is impregnated with the chemical solution (a).
ここで、(a)薬液とは、上記次亜塩素酸水そのものであってもよく、また上記次亜塩素酸水に加えて、前述する薬学的に許容される各種添加成分を含むものであってもよい。 Here, (a) the chemical solution may be the above-mentioned hypochlorous acid water itself, or contains the above-mentioned various pharmaceutically acceptable additive components in addition to the above-mentioned hypochlorous acid water. May be.
また、(b)乾燥ゲルとは、ネイティブ型ジェランガム及び水を含有するヒドロゲル組成物を乾燥させることにより得られるものであり、それ自体ゲルではないが、水分を速やかに吸収して膨潤し、所望の形状安定性（例えば、外用剤としての使用に耐えうる強度や形状保持特性等）を備えながらゲル状を呈することにより、ヒドロゲル組成物となるものである。 In addition, (b) a dry gel is obtained by drying a hydrogel composition containing native gellan gum and water. A hydrogel composition is obtained by exhibiting a gel-like shape while having shape stability (for example, strength and shape-retaining characteristics that can be used as an external preparation).
乾燥ゲルのゲル化剤にネイティブ型ジェランガムを使用することにより、上記次亜塩素酸水に対する吸収力の高い乾燥ゲルを調製することができる。 By using native gellan gum as the gelling agent for the dried gel, a dried gel having a high absorbability for the hypochlorous acid water can be prepared.
当該(b)乾燥ゲルは、以下の工程を経て製造される：(1)ネイティブ型ジェランガム及び水と共に、必要に応じて、前述する他のゲル化剤、カルシウム塩、安定化剤、その他添加成分を混合して加熱し、均一に撹拌し、十分に溶解した後に冷却することによりヒドロゲル組成物を調製する工程、(2)前記ヒドロゲル組成物を乾燥させることにより乾燥ゲルを調製する工程。 The (b) dry gel is produced through the following steps: (1) Along with native gellan gum and water, if necessary, other gelling agents, calcium salts, stabilizers, and other additive components described above A step of preparing a hydrogel composition by mixing, heating, uniformly stirring, sufficiently dissolving and then cooling, and (2) a step of preparing a dry gel by drying the hydrogel composition.
ここで、前記(1)の工程において、ヒドロゲル組成物の水分含量としては、特に制限されないが、該ヒドロゲル組成物の総量に対して９０〜９９．５重量％程度に設定することが望ましい。 Here, in the step (1), the water content of the hydrogel composition is not particularly limited, but is preferably set to about 90 to 99.5% by weight with respect to the total amount of the hydrogel composition.
また、前記(2)の工程において、ヒドロゲル組成物を乾燥させる方法についても、特に制限されず、常法に従うことができるが、具体的には加熱処理等が例示される。なお、当該工程で得られる乾燥ゲルの乾燥の程度は特に制限されない。例えば、乾燥ゲルの水分含量としては、該乾燥ゲルの総量に対して、水分が９０重量％以下、好ましくは４０〜７０重量％を挙げることができる。 In the step (2), the method for drying the hydrogel composition is not particularly limited, and can follow a conventional method. Specific examples include heat treatment. The degree of drying of the dried gel obtained in this step is not particularly limited. For example, the moisture content of the dry gel may be 90% by weight or less, preferably 40 to 70% by weight, based on the total amount of the dry gel.
また、当該(b)乾燥ゲルは、乾燥時の形状の歪みを防止するために、多価アルコール、糖アルコール及び糖類のいずれか少なくとも一種の安定化剤を含有することが好ましい。中でも好ましくはプロピレングリコール及び／又はグリセリンであり、特に好ましくはプロピレングリコールである。 The (b) dry gel preferably contains at least one stabilizer selected from polyhydric alcohols, sugar alcohols and sugars in order to prevent distortion of the shape during drying. Among them, preferred is propylene glycol and / or glycerin, and particularly preferred is propylene glycol.
当該(b)乾燥ゲルは(a)薬液を吸収して膨潤して本発明の医薬組成物になるため、当該(b)乾燥ゲルの形状は、目的とする医薬組成物の形状に対応するように適宜設定される。また、当該乾燥ゲルがシート状である場合、当該乾燥ゲルの一方の面は、前述する支持体が設けられていても良い。 Since the (b) dry gel (a) absorbs the drug solution and swells to become the pharmaceutical composition of the present invention, the shape of the (b) dry gel corresponds to the shape of the intended pharmaceutical composition. Is set as appropriate. Moreover, when the said dry gel is a sheet form, the support body mentioned above may be provided in one side of the said dry gel.
(a)薬液と(b)乾燥ゲルをそれぞれ調製し、所定量の(a)薬液を(b)乾燥ゲルに接触させて含浸させることにより、本発明の医薬組成物を得ることができる。本発明の医薬組成物を調製する際に使用される(a)薬液と(b)乾燥ゲルの比率としては、目的とする医薬組成物の組成に応じて適宜設定されるが、一般的には、(b)乾燥ゲル１重量部に対して(a)薬液が０．１〜１００重量部、好ましくは１〜５０重量部となる比率が採用される。 The pharmaceutical composition of the present invention can be obtained by preparing (a) a drug solution and (b) a dry gel, respectively, and impregnating a predetermined amount of (a) drug solution with (b) the dry gel. The ratio of (a) drug solution and (b) dry gel used in preparing the pharmaceutical composition of the present invention is appropriately set according to the composition of the target pharmaceutical composition, but in general, (B) A ratio of (a) 0.1 to 100 parts by weight, preferably 1 to 50 parts by weight, of the drug solution is employed with respect to 1 part by weight of the dried gel.
このように(a)薬液を(b)乾燥ゲルに含浸させる方法によれば、(a)薬液に含まれる次亜塩素酸水がゲル化剤の溶解のために不可欠な高温条件下に晒されることがなく、(a)薬液中の次亜塩素酸の濃度の低下を招くことがないので、所望濃度の次亜塩素酸を含むヒドロゲル組成物が調製できる。 As described above, according to the method of (a) impregnating the chemical solution with (b) the dry gel, (a) hypochlorous acid water contained in the chemical solution is exposed to high temperature conditions indispensable for dissolving the gelling agent. And (a) the concentration of hypochlorous acid in the chemical solution is not reduced, so that a hydrogel composition containing a desired concentration of hypochlorous acid can be prepared.
なお、本発明の医薬組成物、上記(a)薬液、及び上記(b)乾燥ゲルの製造において、必要に応じて、公知又は慣用されている各種殺菌、滅菌処理を適宜実施してもよい。 In the production of the pharmaceutical composition of the present invention, the above (a) drug solution, and (b) dry gel, various known and commonly used sterilization and sterilization treatments may be appropriately performed as necessary.
２．経皮投与用の医療シート
上記医薬組成物がシート状形態である場合には、該医薬組成物の皮膚に適用される面には吸水性素材を含む吸水層が積層されていてもよい。即ち、吸水性素材を含む吸水層上に上記シート状の医薬組成物が積層されてなる積層シート状剤を、経皮投与用の医療シートとして使用できる。このように、皮膚と医薬組成物との間に吸水層を介在させることによって、上記医薬組成物に含まれる次亜塩素酸水を吸水層を介して患部に供給しながら、患部から生じる滲出液を吸水層により効率的に吸い取ることができるという利点が得られる。即ち、当該医療シートは、患部の滲出液により治療効果が阻害される皮膚潰瘍、例えば褥瘡の治療に、特に有用である。 2. Medical sheet for transdermal administration When the pharmaceutical composition is in sheet form, a water-absorbing layer containing a water-absorbing material may be laminated on the surface of the pharmaceutical composition applied to the skin. That is, a laminated sheet-form preparation obtained by laminating the above sheet-form pharmaceutical composition on a water-absorbent layer containing a water-absorbing material can be used as a medical sheet for transdermal administration. In this way, by interposing a water-absorbing layer between the skin and the pharmaceutical composition, while supplying hypochlorous acid water contained in the pharmaceutical composition to the affected area through the water-absorbing layer, exudate generated from the affected area The advantage is that the water can be efficiently absorbed by the water absorption layer. That is, the medical sheet is particularly useful for the treatment of skin ulcers, for example pressure sores, whose therapeutic effect is hindered by the exudate from the affected area.
当該医療シートにおいて、吸水層に使用される吸水性素材としては、例えば、綿、麻、羊毛などの天然繊維、レーヨンなどのセルロース系繊維、ナイロン、ポリエステル、アクリルなどの合成繊維などを素材とする織布や不織布が挙げられる。また、当該吸水性素材としては、ガーゼ、脱脂綿、ティッシュペーパー、スポンジ等を使用することもできる。当該医療シートにおいて、当該吸水性素材は、皮膚患部に適用する時に当該患部の形状に適合するように伸縮性をある程度有するものが好ましい。当該医療シートにおいて、吸水性素材として好適には医療用のガーゼが挙げられる。 In the medical sheet, examples of the water-absorbing material used for the water-absorbing layer include natural fibers such as cotton, hemp, and wool, cellulose fibers such as rayon, and synthetic fibers such as nylon, polyester, and acrylic. A woven fabric and a nonwoven fabric are mentioned. Moreover, as the water-absorbing material, gauze, absorbent cotton, tissue paper, sponge and the like can be used. In the medical sheet, it is preferable that the water-absorbing material has a certain degree of elasticity so as to conform to the shape of the affected part when applied to the affected part of the skin. In the medical sheet, medical gauze is preferably used as the water-absorbing material.
当該医療シートにおいて、上記吸水層については、その厚さを適切に調整することにより、患部から生じる滲出液を吸収する作用と、次亜塩素酸水を上記医薬組成物から患部へ供給する作用とをバランス良く備えさせることが必要である。上記吸水層の厚さについては、使用する吸水性素材の種類によって異なるが、例えば、上記シート状医薬組成物の厚さの０．０１〜５０倍、好ましくは０．１〜１０倍、更に好ましくは０．１〜２倍、最も好ましくは、０．４〜１倍程度が挙げられる。上記吸水層の厚さが、当該範囲よりも著しく大きい場合には、吸水性素材が乾きやすくなる傾向が現れ、また当該範囲よりも著しく小さい場合には、患部から生じる滲出液を十分に吸収できない傾向が現れる。 In the medical sheet, with respect to the water-absorbing layer, by appropriately adjusting the thickness thereof, an action of absorbing exudate generated from the affected part, and an action of supplying hypochlorous acid water from the pharmaceutical composition to the affected part Must be provided in a well-balanced manner. The thickness of the water-absorbing layer varies depending on the type of water-absorbing material to be used. For example, the thickness of the sheet-form pharmaceutical composition is 0.01 to 50 times, preferably 0.1 to 10 times, more preferably Is 0.1 to 2 times, and most preferably about 0.4 to 1 times. When the thickness of the water-absorbing layer is significantly larger than the range, the water-absorbing material tends to dry, and when the thickness is significantly smaller than the range, the exudate generated from the affected area cannot be sufficiently absorbed. A trend appears.
当該医療シートにおいて、上記吸水層については、自重の１〜１００倍、好ましくは、２〜５０倍、更に好ましくは、５〜３０倍の吸水力を有する吸水性素材で構成されていることが望ましい。このような吸水層と上記医薬組成物とを組み合わせることによって、患部から生じる滲出液を吸収する作用と、次亜塩素酸水を上記医薬組成物から患部へ供給する作用の両作用を効果的に発現させることが可能になる。なお、ここでいう「吸水力」とは、室温で水を最大に吸収させた際に、吸水性素材の重量に対して、該素材に吸収された水の重量の比である。 In the medical sheet, the water-absorbing layer is preferably composed of a water-absorbing material having a water-absorbing force of 1 to 100 times, preferably 2 to 50 times, more preferably 5 to 30 times its own weight. . By combining such a water-absorbing layer and the pharmaceutical composition, both the action of absorbing exudate from the affected area and the action of supplying hypochlorous acid water from the pharmaceutical composition to the affected area are effectively obtained. It can be expressed. Here, “water absorption” is the ratio of the weight of water absorbed by the material to the weight of the water-absorbing material when water is absorbed to the maximum at room temperature.
当該医療シートは、例えば、上記医薬組成物と吸水性素材からなる吸水層とを公知の方法によって積層させることにより調製される。具体的には、当該医療シートの製造方法において、上記医薬組成物は粘着性があるので、結合剤等を使用することなく上記医薬組成物と吸水性素材とを接触させることにより積層させることができる。また、必要に応じて、薬学的に許容される結合剤を介在させて上記医薬組成物と吸水性素材とを積層させてもよい。 The said medical sheet is prepared by laminating | stacking the said pharmaceutical composition and the water absorption layer which consists of a water absorbing material by a well-known method, for example. Specifically, in the manufacturing method of the medical sheet, since the pharmaceutical composition is sticky, it can be laminated by contacting the pharmaceutical composition and the water-absorbing material without using a binder or the like. it can. If necessary, the pharmaceutical composition and the water-absorbing material may be laminated with a pharmaceutically acceptable binder interposed.
また、前述する乾燥ゲルに予め吸水性素材からなる吸水層を積層させておき、当該吸水層が積層された乾燥ゲルを前記(b)乾燥ゲルとして用いて、前述と同様に、所定量の(a)薬液を(b)乾燥ゲルに接触させて含浸させることにより、当該医療シートを得ることができる。 Further, by previously laminating a water-absorbing layer made of a water-absorbing material on the above-mentioned dry gel, and using the dry gel on which the water-absorbing layer is laminated as the (b) dry gel, a predetermined amount ( The medical sheet can be obtained by impregnating (a) the chemical solution with (b) the dried gel.
また、当該医療シートにおいて、上記医薬組成物の吸水層非接触面（即ち、吸水層と接触する面とは反対側の面）に、支持体を設けていてもよい。当該支持体の構成素材、形態等については、上記「１．経皮投与用医薬組成物」の欄に記載する支持体と同様である。 In the medical sheet, a support may be provided on the non-contact surface of the pharmaceutical composition (that is, the surface opposite to the surface in contact with the water absorption layer). The constituent material, form and the like of the support are the same as those of the support described in the column of “1. Pharmaceutical composition for transdermal administration”.
また、当該医療シートの使用時に、上記吸収層に次亜塩素酸水を含浸させて使用すると、皮膚潰瘍の治療効果がより一層効果的に奏されるため、望ましい。ここで、上記吸収層に含浸させる次亜塩素酸水としては、上記医薬組成物で使用される次亜塩素酸水と同様ものが使用される。 In addition, when the medical sheet is used, it is preferable to impregnate the absorbent layer with hypochlorous acid water because the therapeutic effect of skin ulcer is more effectively exhibited. Here, the hypochlorous acid water impregnated in the absorption layer is the same as the hypochlorous acid water used in the pharmaceutical composition.
更に、当該医療シートは、使用時に上記医薬組成物と上記吸水層が積層される限り、使用前は、上記医薬組成物と上記吸水層は分離された状態であってもよい。例えば、当該医療シートの使用形態として、上記吸水層を皮膚患部に貼付し、その上に上記医薬組成物を積層させる方法も含まれる。 Furthermore, as long as the said medical composition and the said water absorption layer are laminated | stacked at the time of use, the said medical sheet may be in the state which the said pharmaceutical composition and the said water absorption layer isolate | separated before use. For example, the usage form of the medical sheet includes a method in which the water-absorbing layer is applied to the affected skin area and the pharmaceutical composition is laminated thereon.
また、当該医療シートの適用対象疾患、使用方法等については、上記「１．経皮投与用医薬組成物」の欄に記載の通りである。 In addition, the disease to which the medical sheet is applied, the method of use, and the like are as described in the column “1. Pharmaceutical composition for transdermal administration”.
３．キット
本発明は、更に、(a)薬液、及び(b)乾燥ゲルを含有する経皮投与用医薬組成物の製造用キットを提供する。当該キットによれば、保存時には上記(a)薬液及び上記(b)乾燥ゲルを分離した状態にしておき、用時に(a)薬液を(b)乾燥ゲルに接触させて含浸させることにより、上記経皮投与用医薬組成物を簡便に調製することが可能になる。 3. Kit The present invention further provides a kit for producing a pharmaceutical composition for transdermal administration containing (a) a drug solution and (b) a dried gel. According to the kit, the (a) chemical solution and the (b) dry gel are kept separated during storage, and the (a) chemical solution is contacted with the dry gel (b) and impregnated during use. A pharmaceutical composition for transdermal administration can be easily prepared.
当該キットでは、１回当たり使用される量の(a)薬液及び(b)乾燥ゲルをそれぞれ区分けしておくことが好ましい。 In the kit, it is preferable to separate the amount of (a) chemical solution and (b) dry gel used each time.
このように、保存時には上記(a)薬液及び上記(b)乾燥ゲルを分離した状態にしておくと、予めゲル化させた場合に比べて容積が小さいため、持ち運び、取り扱い、保管等が簡便になる。 As described above, when the (a) chemical solution and the (b) dry gel are separated during storage, the volume is smaller than when the gel is preliminarily gelled. Become.
４．皮膚潰瘍の治療方法
前述するように、上記経皮投与用医薬組成物、又は上記経皮投与用の医療シートは、皮膚潰瘍の治療、特に褥瘡の治療に有用である。従って、本発明は、更に他の観点から、皮膚潰瘍患者の皮膚潰瘍患部に、上記経皮投与用医薬組成物、又は上記医療シートを適用することを特徴とする、皮膚潰瘍の治療方法を提供する。また、本発明は、上記経皮投与用医薬組成物の、皮膚潰瘍治療剤の製造のための使用を提供する。更に、本発明は、上記経皮投与用の医療シートの、皮膚潰瘍治療剤の製造のための使用を提供する。 4). Method for treating skin ulcer As described above, the pharmaceutical composition for transdermal administration or the medical sheet for transdermal administration is useful for the treatment of skin ulcer, particularly the treatment of pressure ulcer. Accordingly, the present invention provides a method for treating skin ulcers, characterized in that the pharmaceutical composition for transdermal administration or the medical sheet is applied to a skin ulcer affected area of a skin ulcer patient from still another viewpoint. To do. The present invention also provides use of the pharmaceutical composition for transdermal administration for the production of a skin ulcer therapeutic agent. Furthermore, the present invention provides the use of the medical sheet for transdermal administration for the production of a skin ulcer therapeutic agent.
これらの治療方法及び使用において、具体的実施形態については、上記「１．経皮投与用医薬組成物」及び「２．経皮投与用の医療シート」の欄に記載の通りである。 In these treatment methods and uses, specific embodiments are as described in the columns of “1. Pharmaceutical composition for transdermal administration” and “2. Medical sheet for transdermal administration”.
以下、本発明の内容を以下の実施例を用いて具体的に説明するが、本発明はこれらに何ら限定されるものではない。なお、以下に実施例において、ネイティブ型ジェランガムは、ケルコゲルHT（三栄源エフ・エフ・アイ株式会社製）を使用し、脱アシル型ジェランガムはケルコゲル（食品用ジェランガム）（三栄源エフ・エフ・アイ株式会社製）を使用した。 Hereinafter, the content of the present invention will be specifically described with reference to the following examples, but the present invention is not limited thereto. In the following examples, Kelco Gel HT (manufactured by Saneigen FFI Co., Ltd.) is used as the native gellan gum, and Kelcogel (food grade gellan gum) (Saneigen FFI Corporation) is used as the deacylated gellan gum. Used).
実施例１−４ 経皮投与用医薬組成物の物性評価
（１）乾燥ゲルの調製
表１に示す処方の乾燥ゲル（実施例用乾燥ゲル１−４、比較例用乾燥ゲル１−１０；何れも厚さ０．２〜０．４mmのシート状）を以下の方法に従って調製した。 Example 1-4 Evaluation of Physical Properties of Pharmaceutical Composition for Transdermal Administration (1) Preparation of Dry Gel Dry gels of the formulations shown in Table 1 (Example Dry Gel 1-4, Comparative Example Dry Gel 1-10; Was also prepared according to the following method.
＜乾燥ゲルの調製方法＞
実施例用乾燥ゲル１−４、比較例用乾燥ゲル１−３及び５−９の場合
１．85℃のイオン交換水360gに、所定量のゲル化剤を少量ずつ添加し、85℃にて10分間加熱攪拌溶解した。
２．少量の85℃のイオン交換水に溶解した乳酸カルシウム又は塩化カリウムの粉末を所定量添加した。
３．プロピレングリコールを所定量添加した。
４．加熱により蒸発した水を補うため、85℃のイオン交換水を適量加えて全量を400gに調整した。
５．90mm×90mmのシャーレに上記４で得られた溶液を30g充填し、5℃の冷蔵庫にて約2時間静置して、含水ゲルを調製した。
６．得られたヒドロゲルを50℃の乾燥機にて7時間乾燥して、乾燥ゲルを調製した。<Method for preparing dry gel>
In the case of the dry gel 1-4 for examples and the dry gels 1-3 and 5-9 for comparative examples 1. A predetermined amount of gelling agent was added little by little to 360 g of ion-exchanged water at 1.85 ° C. The mixture was dissolved with heating and stirring for 10 minutes.
2. A predetermined amount of calcium lactate or potassium chloride powder dissolved in a small amount of ion exchange water at 85 ° C. was added.
3. A predetermined amount of propylene glycol was added.
4). In order to compensate for water evaporated by heating, an appropriate amount of 85 ° C. ion exchange water was added to adjust the total amount to 400 g.
5. A petri dish of 90 mm × 90 mm was filled with 30 g of the solution obtained in 4 above and allowed to stand in a refrigerator at 5 ° C. for about 2 hours to prepare a hydrous gel.
6). The obtained hydrogel was dried in a dryer at 50 ° C. for 7 hours to prepare a dried gel.
比較例用乾燥ゲル４の場合
１．20℃のイオン交換水360gに、所定量のガラクトマンナンを少量ずつ添加し、20℃にて10分間攪拌した。
２．85℃まで加熱し、所定量のカラギナンを少量ずつ添加して、85℃にて10分間加熱攪拌した。
３．塩化カリウムの粉末を所定量添加した。
４．プロピレングリコールを所定量添加した。
５．加熱により蒸発した水を補うため、85℃のイオン交換水を適量加えて全量を400gに調整して、ヒドロゲルを調製した。
６．90mm×90mmのシャーレに上記５で得られた溶液を30g充填し、5℃の冷蔵庫にて約2時間静置して、含水ゲルを調製した。
７．50℃の乾燥機にて7時間乾燥して、乾燥ゲルを調製した。 In the case of the comparative dry gel 4, 1. A predetermined amount of galactomannan was added little by little to 360 g of ion-exchanged water at 20 ° C., and the mixture was stirred at 20 ° C. for 10 minutes.
2. Heated to 85 ° C., a predetermined amount of carrageenan was added little by little, and the mixture was heated and stirred at 85 ° C. for 10 minutes.
3. A predetermined amount of potassium chloride powder was added.
4). A predetermined amount of propylene glycol was added.
5. In order to make up for the water evaporated by heating, an appropriate amount of 85 ° C. ion exchange water was added to adjust the total amount to 400 g to prepare a hydrogel.
6. A petri dish of 90 mm × 90 mm was filled with 30 g of the solution obtained in 5 above and allowed to stand in a refrigerator at 5 ° C. for about 2 hours to prepare a hydrous gel.
7. Dried for 7 hours in a dryer at 50 ° C. to prepare a dried gel.
比較例用乾燥ゲル１０の場合
１．85℃のイオン交換水360gに、所定量のゲル化剤を少量ずつ添加し、85℃にて10分間加熱攪拌溶解した。
２．炭酸カルシウムを所定量添加した。
３．グルコノデルタラクトンを所定量添加した。
４．プロピレングリコールを所定量添加した。
５．加熱により蒸発した水を補うため、85℃のイオン交換水を適量加えて全量を400gに調整した。
６．90mm×90mmのシャーレに上記５で得られた溶液を30g充填し、5℃の冷蔵庫にて約2時間静置して、ヒドロゲルを調製した。
７．50℃の乾燥機にて7時間乾燥して、乾燥ゲルを調製した。 In the case of the comparative dry gel 10 , a predetermined amount of gelling agent was added little by little to 360 g of ion-exchanged water at 1.85 ° C., and the mixture was dissolved by stirring at 85 ° C. for 10 minutes.
2. A predetermined amount of calcium carbonate was added.
3. A predetermined amount of glucono delta lactone was added.
4). A predetermined amount of propylene glycol was added.
5. In order to compensate for water evaporated by heating, an appropriate amount of 85 ° C. ion exchange water was added to adjust the total amount to 400 g.
6. A 90 mm × 90 mm petri dish was filled with 30 g of the solution obtained in 5 above and allowed to stand in a refrigerator at 5 ° C. for about 2 hours to prepare a hydrogel.
7. Dried for 7 hours in a dryer at 50 ° C. to prepare a dried gel.
（２）乾燥ゲルの物性評価
上記（１）で得られた各乾燥ゲルについて物性評価を行った。物性評価における評価項目、判定方法、判定基準については、表２に示す通りである。なお、以下に示す「強酸性電解水」とは、有効塩素濃度55ppmでpH2.7の次亜塩素酸水であり、「弱酸性電解水」とは有効塩素濃度30ppmでpH5.7の次亜塩素酸水である。(2) Physical property evaluation of dry gel Physical property evaluation was performed about each dry gel obtained by said (1). Evaluation items, determination methods, and determination criteria in the physical property evaluation are as shown in Table 2. The “strongly acidic electrolyzed water” shown below is hypochlorous acid water having an effective chlorine concentration of 55 ppm and a pH of 2.7, and the “weakly acidic electrolyzed water” is the hypochlorous acid water having an effective chlorine concentration of 30 ppm and a pH of 5.7. Chloric acid water.
得られた結果を表３−５に示す。この結果から、ネイティブ型ジェランガムを使用すると、歪みのないシート状の乾燥ゲルが調製できることが確認された。また、ネイティブ型ジェランガムと次亜塩素酸水を併用してゲルを調製すると、全ての評価項目で良好な結果が得られた。一方、ゲル化剤として、ネイティブ型ジェランガム以外を使用した乾燥ゲル（比較乾燥ゲル１−１０）は、いずれも所望の物性が得られなかった。 The obtained results are shown in Table 3-5. From this result, it was confirmed that when native gellan gum was used, a sheet-like dry gel without distortion could be prepared. Moreover, when a gel was prepared using both native gellan gum and hypochlorous acid water, good results were obtained for all evaluation items. On the other hand, none of the dry gels (comparative dry gel 1-10) using a gelling agent other than native gellan gum had desired physical properties.
試験例１ 殺菌効果持続性の評価
実施例用乾燥ゲル２（10cm×10cm、厚さ0.4mm）に200gの強酸性電解水を添加して、室温で15分間静置し、ヒドロゲル組成物（経皮投与用医薬組成物；11cm×11cm、厚さ0.2cm）を調製した。また、滅菌ガーゼ（10cm×10cm、厚さ0.2cm）を200gの強酸性電解水（有効塩素濃度55ppmでpH2.7の次亜塩素酸水）に十分に浸したものを調製した。当該ヒドロゲル組成物及びガーゼについて、殺菌効果持続性について評価した。具体的には、当該ヒドロゲル組成物と滅菌ガーゼを温度25℃、相対湿度40〜50％の条件下で３時間放置し、当該ヒドロゲル組成物と滅菌ガーゼに残存する有効塩素濃度を経時的に測定した。 Test Example 1 Evaluation of Sustainability of Bactericidal Effect 200 g of strongly acidic electrolyzed water was added to the dried gel 2 for Example (10 cm × 10 cm, thickness 0.4 mm) and allowed to stand at room temperature for 15 minutes. A pharmaceutical composition for skin administration; 11 cm × 11 cm, thickness 0.2 cm) was prepared. A sterilized gauze (10 cm × 10 cm, thickness 0.2 cm) was prepared by sufficiently immersing it in 200 g of strongly acidic electrolyzed water (hypochlorous acid water having an effective chlorine concentration of 55 ppm and a pH of 2.7). The hydrogel composition and the gauze were evaluated for bactericidal effect persistence. Specifically, the hydrogel composition and sterilized gauze are allowed to stand for 3 hours under conditions of a temperature of 25 ° C. and a relative humidity of 40-50%, and the effective chlorine concentration remaining in the hydrogel composition and sterilized gauze is measured over time. did.
その結果、滅菌ガーゼについては１５分後には有効塩素が消失し、殺菌効力を失なわれた。これに対して、上記ヒドロゲル組成物では３時間経過後も有効塩素が残存しており、殺菌効力が維持されていることが判った。 As a result, the effective chlorine disappeared after 15 minutes for the sterilized gauze, and the bactericidal efficacy was lost. On the other hand, in the said hydrogel composition, it turned out that effective chlorine remains even after 3 hours, and the bactericidal effect is maintained.
試験例２ 褥瘡治療効果の評価
1.2ｇの実施例用乾燥ゲル２に、20gの強酸性電解水（有効塩素濃度55ppmでpH2.7の次亜塩素酸水）を加えて室温で15分間静置し、厚さ約2mmのシート状のヒドロゲル組成物（経皮投与用医薬組成物）を調製した。 Test Example 2 Evaluation of pressure ulcer treatment effect
Add 20 g of strongly acidic electrolyzed water (effective chlorine concentration 55 ppm and pH 2.7 hypochlorous acid water) to 1.2 g of dry gel 2 for Example, and let stand at room temperature for 15 minutes. A hydrogel composition (a pharmaceutical composition for transdermal administration) was prepared.
このヒドロゲル組成物を用いて、複数箇所の褥瘡部位を有する被験者1名にて褥瘡の治療効果を評価した。具体的には、ヒドロゲル組成物を褥瘡部位に対して、1日1回交換しながら２週間貼付し続けた。なお、治療期間中、褥瘡部位に貼付したヒドロゲル組成物の上に医療用ガーゼを被せ、これをメディカルテープで固定しておいた。 Using this hydrogel composition, the therapeutic effect of pressure ulcer was evaluated in one subject having multiple pressure ulcer sites. Specifically, the hydrogel composition was continuously applied to the pressure ulcer site for 2 weeks while changing once a day. During the treatment period, a medical gauze was placed on the hydrogel composition affixed to the pressure ulcer site, and this was fixed with a medical tape.
この結果、ヒドロゲル組成物による優れた褥瘡の治療効果が認められた。また、ヒドロゲル組成物は、患部への付着性も高く、更には脱着時の剥離も容易であることも確認された。 As a result, an excellent therapeutic effect for pressure sores by the hydrogel composition was recognized. Moreover, it was also confirmed that the hydrogel composition has high adhesion to the affected area and is easy to peel off at the time of desorption.
試験例３ 褥瘡治療効果の評価
以下の条件で、褥瘡患者の治療を実施した。
１．患者
７０才代女性褥瘡患者。当該患者の褥瘡症状は、皮下組織にも及ぶ損傷があり、褥瘡部位の長径が約５０ｍｍであり、良性肉芽が創面の１０％未満である。また、褥瘡には、多量の滲出液がみられ、１日２回以上のドレッシング交換や消毒などの処置を要するレベルであった。 Test Example 3 Evaluation of pressure ulcer treatment effect Treatment of pressure ulcer patients was performed under the following conditions.
1. Patient 70s female pressure ulcer patient. The pressure ulcer symptoms of the patient include damage to the subcutaneous tissue, the major axis of the pressure ulcer site is about 50 mm, and the benign granulation is less than 10% of the wound surface. In addition, a large amount of exudate was seen in pressure ulcers, and it was a level that required treatment such as dressing change and disinfection at least twice a day.
２．治療剤の調製
強酸性電解水含有ガーゼ
医療用の滅菌ガーゼ（綿100％；吸水力：室温で自重の10.6倍；10cm×10cm、厚さ0.2cm）に、強酸性電解水（有効塩素濃度55ppmでpH2.7の次亜塩素酸水）を含ませることにより、強酸性電解水含有ガーゼを調製した。 2. Preparation of therapeutic agent
Strong acid electrolyzed water-containing gauze medical sterilized gauze (cotton 100%; water absorption: 10.6 times its own weight at room temperature; 10 cm x 10 cm, thickness 0.2 cm), strongly acidic electrolyzed water (effective chlorine concentration 55 ppm, pH 2.7) In addition, a strongly acidic electrolyzed water-containing gauze was prepared.
医療シート
消毒済の容器に容器底面から約1cmの高さまで、強酸性電解水（有効塩素濃度55ppmでpH2.7の次亜塩素酸水）を入れ、これに、滅菌済の実施例用乾燥ゲル２（10cm×10cm、厚さ0.4mm）を５分間浸漬してシート状のヒドロゲル組成物（医薬組成物）を調製した。当該シート状のヒドロゲル組成物上に、上記強酸性電解水含有ガーゼを設置することにより、医療シートを調製した。A highly acidic electrolyzed water (hypochlorous acid water with an effective chlorine concentration of 55 ppm and pH 2.7) is placed in a medical sheet disinfected container up to a height of about 1 cm from the bottom of the container. 2 (10 cm × 10 cm, thickness 0.4 mm) was immersed for 5 minutes to prepare a sheet-like hydrogel composition (pharmaceutical composition). A medical sheet was prepared by installing the strongly acidic electrolyzed water-containing gauze on the sheet-like hydrogel composition.
３．治療スケジュール及び治療結果
上記患者の褥瘡部位に、強酸性電解水含有ガーゼを貼付して２週間処置した。処置期間中は、強酸性電解水含有ガーゼを、１日２回（午前と午後）、新しいものに交換した。このように強酸性電解水含有ガーゼで処置しても、2週間経過後も褥瘡の治癒傾向は見られなかった。 3. Treatment schedule and treatment results A strong acidic electrolyzed water-containing gauze was applied to the pressure ulcer site of the patient and treated for 2 weeks. During the treatment period, the strongly acidic electrolyzed water-containing gauze was replaced with a new one twice a day (morning and afternoon). Thus, even when treated with gauze containing strongly acidic electrolyzed water, no pressure ulcer healing tendency was observed even after 2 weeks.
強酸性電解水含有ガーゼによる処置の後に、患者の褥瘡部位に上記医療シートを貼付して２週間処置した。処置期間中は、医療シートを、１日２回（午前と午後）、新しいものに交換した。なお、上記医療シートは、強酸性電解水含有ガーゼ側が褥瘡部位に接するように適用した。また、処置期間中、褥瘡部位に貼付した医療シートの上に滅菌ガーゼを被せ、これをメディカルテープで固定しておいた。その結果、２週間後には、褥瘡の大きさが長径約35mmまで縮小していた。更に、２週間後の肉芽組織については、良性肉芽が創面の50％以上になるまで回復していた。 After the treatment with the strongly acidic electrolyzed water-containing gauze, the medical sheet was affixed to the pressure ulcer site of the patient and treated for 2 weeks. During the treatment period, the medical sheet was replaced with a new one twice a day (morning and afternoon). In addition, the said medical sheet was applied so that the strongly acidic electrolyzed water containing gauze side might touch the pressure ulcer site | part. Further, during the treatment period, a sterilized gauze was put on a medical sheet affixed to the pressure ulcer site, and this was fixed with a medical tape. As a result, after 2 weeks, the size of the pressure ulcer was reduced to a major axis of about 35 mm. Furthermore, the granulation tissue after 2 weeks had recovered until the benign granulation reached 50% or more of the wound surface.
試験例４ 褥瘡治療効果の評価
以下の条件で、褥瘡患者の治療を実施した。
１．患者
９０才代女性の褥瘡患者。当該患者の褥瘡症状は、皮下組織にも及ぶ損傷があり、褥瘡部位の長径が約50mm、局所の炎症徴候が見られ、良性肉芽がまったく形成されていない。また、褥瘡には、多量の滲出液がみられ、１日２回以上のドレッシング交換や消毒などの処置を要するレベルであった。 Test Example 4 Evaluation of pressure ulcer treatment effect Treatment of pressure ulcer patients was performed under the following conditions.
1. A 90-year-old female acne patient. The pressure ulcer symptoms of the patient include damage to the subcutaneous tissue, the major axis of the pressure ulcer site is about 50 mm, local signs of inflammation are seen, and no benign granulation is formed. In addition, a large amount of exudate was seen in pressure ulcers, and it was a level that required treatment such as dressing change and disinfection at least twice a day.
２．治療剤の調製
上記試験例３と同様の方法で、強酸性電解水含有ガーゼ、及び医療シートを調製した。 2. Preparation of therapeutic agent A strongly acidic electrolyzed water-containing gauze and a medical sheet were prepared in the same manner as in Test Example 3 above.
３．治療スケジュール及び治療結果
上記患者の褥瘡部位に、強酸性電解水含有ガーゼを貼付して２週間処置した。処置期間中は、強酸性電解水含有ガーゼを、１日２回（午前と午後）、新しいものに交換した。このように強酸性電解水含有ガーゼで処置しても、2週間経過後も褥瘡の治癒傾向は見られなかった。 3. Treatment schedule and treatment results A strong acidic electrolyzed water-containing gauze was applied to the pressure ulcer site of the patient and treated for 2 weeks. During the treatment period, the strongly acidic electrolyzed water-containing gauze was replaced with a new one twice a day (morning and afternoon). Thus, even when treated with gauze containing strongly acidic electrolyzed water, no pressure ulcer healing tendency was observed even after 2 weeks.
強酸性電解水含有ガーゼによる処置の後に、患者の褥瘡部位に上記医療シートを貼付して２週間処置した。褥瘡部位に適用した医療シートの上に、更に滅菌ガーゼを被せて、これをメディカルテープで固定した。処置期間中は、医療シートを、１日２回（午前と午後）、新しいものに交換した。なお、上記医療シートは、強酸性電解水含有ガーゼ側が褥瘡部位に接するように適用した。その結果、２週間後には、褥瘡の大きさが顕著に縮小し、局所の炎症兆候が全くなくなっていた。更に、２週間後の肉芽組織については、良性肉芽が創面の４０％程度になるまで回復していた。 After the treatment with the strongly acidic electrolyzed water-containing gauze, the medical sheet was affixed to the pressure ulcer site of the patient and treated for 2 weeks. The medical sheet applied to the pressure ulcer site was further covered with sterilized gauze and fixed with medical tape. During the treatment period, the medical sheet was replaced with a new one twice a day (morning and afternoon). In addition, the said medical sheet was applied so that the strongly acidic electrolyzed water containing gauze side might touch the pressure ulcer site | part. As a result, after 2 weeks, the size of the pressure ulcer was remarkably reduced and there was no sign of local inflammation. Further, the granulation tissue after 2 weeks had recovered until the benign granulation reached about 40% of the wound surface.
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| JP2002104974A (en) * | 2000-09-29 | 2002-04-10 | Nichiban Co Ltd | Hydrogel therapeutic agent for damaged skin |
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