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WO1993012818A1 - Preparation pharmaceutique pour application topique - Google Patents

Preparation pharmaceutique pour application topique Download PDF

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Publication number
WO1993012818A1
WO1993012818A1 PCT/JP1992/001684 JP9201684W WO9312818A1 WO 1993012818 A1 WO1993012818 A1 WO 1993012818A1 JP 9201684 W JP9201684 W JP 9201684W WO 9312818 A1 WO9312818 A1 WO 9312818A1
Authority
WO
WIPO (PCT)
Prior art keywords
agent
preparation
drug
superabsorbent polymer
polymer
Prior art date
Application number
PCT/JP1992/001684
Other languages
English (en)
Japanese (ja)
Inventor
Koichi Oshima
Yasuo Morita
Sumie Seki
Tadanori Morikawa
Eiichi Mafune
Original Assignee
Daiichi Pharmaceutical Co., Ltd.
Fuji Yakuhin Kogyo Kabushiki Kaisha
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Daiichi Pharmaceutical Co., Ltd., Fuji Yakuhin Kogyo Kabushiki Kaisha filed Critical Daiichi Pharmaceutical Co., Ltd.
Publication of WO1993012818A1 publication Critical patent/WO1993012818A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions

Definitions

  • the present invention provides a topical preparation, more specifically, a drug that is retained in a superabsorbent polymer, is stable, does not stick, or leaks, is easy to remove and clean after application to an affected area, and It relates to a topical preparation that allows easy control of the amount of drug.
  • liquids, aerosols, ointments, plasters, cataplasms, vaginals, suppositories, and the like are used to treat skin diseases, vaginal and hemorrhoids, and the like. All of these are preparations in which an appropriate base and drug are uniformly mixed and applied as it is or molded into a fixed shape, or applied by spreading on cloth, paper, or plastic film. .
  • the stability of the drug is good, it does not have stickiness and does not cause leakage, it is easy to adjust the amount of drug, it is easy to remove and clean after application, and it is easy to use, skin diseases, vaginal diseases, It has been desired to develop a topical preparation that can be used for diseases such as hemorrhoids.
  • the present inventors have conducted intensive studies and found that the drug held in the superabsorbent polymer is unexpectedly released out of the polymer by the moisture absorbed by the superabsorbent polymer.
  • the present inventor has discovered and found that the above problem can be solved by using this, and completed the present invention.
  • the present invention provides a topical preparation comprising a superabsorbent polymer holding a drug.
  • topical preparation of the present invention refers to a topical preparation used for the treatment of so-called athlete's foot and insects, as well as an external preparation used by coating or pasting for the treatment of ordinary skin diseases. It also includes preparations to be used, or preparations that absorb drugs from mucous membranes such as vaginal preparations, suppositories, nasal absorption preparations, and ear absorption preparations.
  • the superabsorbent polymer used in the present invention preferably has a water absorption of 50 ml or more per gram of the polymer, and more preferably has a water absorption of 100 ml or more.
  • examples of such superabsorbent polymers include starches such as starch Z acrylonitrile, starch carboxymethylated starch, celluloses such as cellulose acrylonitrile, carboxymethylated cellulose, polyacrylic acid, polyvinyl alcohol, polyacrylamide, A synthetic polymer such as polyoxyethylene, poly (vinyl alcohol) polyacrylate, polyacrylic acid Z polyacrylamide, polyacrylamide Z polyvinyl alcohol, or a force capable of using any of two or more selected polymers.
  • polyacryloleic acid ⁇ m polyvinyl alcohol-based, polyacrylamide-based, polyoxyethylene-based synthetic polymer, or a mixed polymer of two or more selected from these are preferred.
  • High absorption Commercially available aqueous polymers can be used, such as Lansir-F (Toyobo), Arrasorp (Arakawa Chemical), Wondergel (Kao), San Diego (Sanyo Chemical), Sumikagel (Sumitomo Chemical), Aqualic (Nippon Shokubai Chemical) ), Lansir (Nippon Xelan), etc. can be used.
  • the form of the superabsorbent polymer is not particularly limited, and may be in the form of a powder, a film, a nonwoven fabric, a fiber, or the like, depending on the purpose of use and the site of use.
  • the drug used in the present invention is preferably a solid drug at room temperature, and the drug used varies depending on the purpose and site of use.
  • antibiotics for example, antibiotics, antibacterial agents, antiviral agents, Fungicides, anticancer agents, anti-inflammatory agents, antihistamines, antirheumatic agents, gout treatments, hormones, inotropic agents, antiarrhythmic agents, angina treatment agents, vasodilators, antihypertensive agents, vasopressors, diuretics, bronchodilators Agents, bronchial asthma treatments, respiratory stimulants, antitussives, expectorants, ulcer treatments, antipyretic analgesics, sleeping pills, autonomic nervous system drugs, ENT, dermatological, urinary and reproductive agents And uterus preparations, therapeutic agents for hemorrhoidal diseases, vitamins and the like.
  • the topical preparation of the present invention may be used, for example, in the form of a powder, film, nonwoven fabric or fiber containing a superabsorbent polymer as it is or appropriately in accordance with its intended use (for example, when it is used in close contact between the hands and toes, a finger pad is used).
  • Shape, vaginal or suppository, tampon-like, nasal-absorbing preparation, nasal plug-like) absorb an aqueous solution of the drug at an appropriate concentration, and then freeze It can be manufactured by removing only water by a method such as drying and keeping the drug uniformly in the superabsorbent polymer. it can.
  • the drug to be used When the drug to be used is insoluble or hardly soluble in water, the drug is dissolved in an organic solvent such as alcohol and absorbed in a molded superabsorbent polymer.
  • the topical preparation of the present invention can be produced by uniformly retaining the drug in the water-absorbing polymer.
  • the superabsorbent polymer holding the drug obtained above may be covered with a nonwoven fabric, woven fabric or sheet made of the same or different material on the front and back. It can also be used.
  • the amount of the drug retained in the superabsorbent polymer depends on the type of the drug, the purpose of use and the site of use, and usually 1 ⁇ g to lg, preferably 1 to 1 g of the superabsorbent polymer. It is about 0 g to 50 O mg.
  • the topical formulation of the present invention thus obtained can block the drug from moisture even during storage and stabilize water-unstable drugs. Can keep power.
  • the topical preparation of the present invention can be used as it is or by cutting it into an appropriate size at the time of use, and applying, pasting or inserting it onto a local disease or site, and exuding the superabsorbent polymer in the topical preparation
  • the affected area is kept clean, and even if the absorbed exudate, secretory fluid, body fluid, etc. are minimal, the drug force is released from the topical preparation by this, It can exhibit the effect of making everything.
  • topical preparation of the present invention can be used regardless of whether it is intended for local action or systemic action. Expecting release effect Wear. Furthermore, since the base does not remain in the affected area when removing the topical preparation of the present invention, it is easy to remove and clean the affected area, it can be removed at any time during the course, and emergency treatment is easy. The amount of drug can also be controlled at any time.
  • topical preparation of the present invention may contain one or more drugs suitable for therapeutic purposes, as well as stabilizers (for example, dextrin, dextran, ⁇ , ⁇ , arcyclodextrin, Hydral talcite, etc.).
  • stabilizers for example, dextrin, dextran, ⁇ , ⁇ , arcyclodextrin, Hydral talcite, etc.
  • Absorption enhancers eg, surfactants such as disodium ethylenediaminetetraacetate, tartaric acid, cunic acid, succinic acid, L-ascorbic acid, etc.
  • preservatives eg, benzalkonium chloride, benzozetonium chloride, ⁇ -1 Naphthol, thimerosal, thymol, etc.
  • dispersants eg, lactose, tragacanth powder, starch, precipitated calcium carbonate, etc.
  • a nonwoven fabric containing 70% of a 3 mm x 3 cm acrylyl fiber hydrolyzate superabsorbent polymer (Lancy Lue F, manufactured by Toyobo Co., Ltd.) of 4 mm thickness is placed on polyethylene (4 cm x 4 cm). Then, 3 ml of an aqueous solution of D Be AMP (1 OmgZml) was absorbed. After water was removed by freeze-drying, the polyethylene sheet under the cover was covered with a polyester non-woven fabric (4 cm ⁇ 4 cm), and the four sides were heat-sealed to obtain a superabsorbent polymer preparation holding DBcAMP.
  • Polyethylene sheet (4 cm x 4 cm) contains 70% of 3 mm x 3 cm acrylyl fiber hydrolyzate superabsorbent polymer (Ransil-1F, manufactured by Toyo Seimitsu Co., Ltd.) of 4 mm thickness Then, 3 ml of an aqueous solution of DMN (1 Omg / ml) was absorbed therein. After removing water by freeze-drying, polyester non-woven fabric (4 cm x 4 cm) Then, the lower polyethylene sheet and the four sides were heat-sealed to obtain a highly water-absorbing polymer preparation retaining DMN.
  • Ransil-1F manufactured by Toyo Seimitsu Co., Ltd.
  • the product was covered with a polyester nonwoven fabric (4 cm x 4 cm), and the lower polyethylene sheet and the four sides were heat-sealed to obtain a superabsorbent polymer preparation holding ofloxacin.
  • a nonwoven fabric containing 70% of a 3 mm x 3 cm acrylyl fiber hydrolyzate superabsorbent polymer (Ranchi F, manufactured by Toyobo Co., Ltd.) of 4 mm thickness on a polyethylene sheet (4 cm x 4 cm) It was placed on it, and 3 ml of an aqueous suspension of ofloxacin (1 Omg / ml) was absorbed. After water was removed by freeze-drying, the resulting product was covered with a polyester non-woven fabric (4 cm x 4 cm), and the lower polyethylene sheet and four sides were heat-sealed to obtain a superabsorbent polymer formulation holding ofloxacin.
  • Polyethylene sheet (4 cm x 4 cm) contains 70% of a 4 mm thick, 3 cm x 3 cm hydrolyzate of ataryl fiber-based superabsorbent polymer (Lansil-F, manufactured by Toyobo Co., Ltd.) Place the non-woven fabric and Then, 3 ml of an aqueous solution (10 mgZml) of poly [(2-oxo-111-pyrrolidyl) ethylene] diodyne (generic name: povidone) as a disinfectant was absorbed.
  • ataryl fiber-based superabsorbent polymer Liansil-F, manufactured by Toyobo Co., Ltd.
  • the resulting product was covered with a polyester non-woven fabric (4 cm x 4 cm), and the lower polyethylene sheet and four sides were heat-sealed to obtain a superabsorbent polymer formulation that retained povidonoxide.
  • Powdered polyacrylate crosslinked superabsorbent polymer is molded into a 3 mm x 30 mm column and absorbs an aqueous solution (0.5 mg / m1) of synthetic calcitonin derivative, elcatonin (0.2 m1).
  • the water was removed by lyophilization to obtain a superabsorbent polymer preparation (vaginal preparation for rats) retaining L-potency.
  • Example 1 A storage test was performed on the preparation obtained in Example 1 and the DBC AMP ointment in a constant temperature bath at 40 ° C. After 1 to 3 months, the content of DBcAMP was quantified by liquid chromatography (reverse phase column HPLC, 11 ⁇ detection of 25411111). The results are shown in Table 1. The results in Table 1 show that the product of the present invention has excellent stability of DB c AMP.
  • Example 27 Eight Kim towels (Jujo Kimberly Co., Ltd .; 3 cm x 3 cm) were uniformly wetted with 1 ml of water. The preparation obtained in Example 1 was placed on a wet Kim towel and fixed with tape, and the Kim towel was replaced with time. DB c AMP was extracted from each Kim towel and quantified using an ultraviolet absorption spectrophotometer (manufactured by Shimadzu: UV-160, measurement wavelength 254 nm). Was. The formulation obtained in Example 27 was also tested in the same manner as described above. (Measurement wavelength: Example 2: 254 nm, Examples 3 and 4: 264 nm, Hife examples 5 and 6: 287 nm, Example 7: 222 nm) did.
  • a drug release test of the preparation obtained in Example 2 was performed using a rat stratum corneum exfoliation model.
  • Example 2 was separated by repeatedly applying and removing a gum tape to the abdominal skin 20 times under urethane anesthesia.
  • the preparation of Example 2 was stuck to the stratum corneum It was fixed with plaster.
  • blood was collected from the jugular vein by heparin, and the amount of unchanged substance in plasma was determined by liquid chromatography (reverse-phase HPLC, 11 ⁇ detection of 2541111). did.
  • the preparation of Example 2 was applied and fixed with a bandage, and the test was performed in the same manner as described above. Table 3 shows the results.
  • a drug release test of the preparations obtained in Examples 9 and 10 was performed using rats.
  • the topical preparation of the present invention can stably hold a drug, easily adjust the amount of a drug, and impart sustained release.
  • the affected area can be kept clean and it is not necessary to remove excess base material, so that it is easy to receive and can be widely used as a topical preparation.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

Préparation pharmaceutique pour application topique comprenant un médicament retenu par un polymère présentant un fort pouvoir d'absorption d'eau. Ce polymère peut retenir le médicament de manière stable, facilite la régulation d'une dose et permet une libération entretenue. Etant donné qu'il n'est pas collant et qu'il ne présente pas d'exsudation, il permet de maintenir propre la partie à traiter; en outre, l'élimination de la base excessive n'est pas nécessaire, ce qui facilite les soins et élargit le champ d'application de cette préparation.
PCT/JP1992/001684 1991-12-27 1992-12-22 Preparation pharmaceutique pour application topique WO1993012818A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP3/346578 1991-12-27
JP34657891 1991-12-27

Publications (1)

Publication Number Publication Date
WO1993012818A1 true WO1993012818A1 (fr) 1993-07-08

Family

ID=18384373

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1992/001684 WO1993012818A1 (fr) 1991-12-27 1992-12-22 Preparation pharmaceutique pour application topique

Country Status (2)

Country Link
JP (1) JPH05246841A (fr)
WO (1) WO1993012818A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997045104A1 (fr) * 1996-05-31 1997-12-04 Fuji Yakuhin Kogyo Kabushiki Kaisha Fibre ayant une capacite elevee d'absorption de l'eau et contenant de l'iode

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2020273810B2 (en) * 2019-05-16 2025-10-09 Shin Nippon Biomedical Laboratories, Ltd. Powder formulation for intranasal administration, and manufacturing method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56103112A (en) * 1980-01-18 1981-08-18 Nippon Synthetic Chem Ind Co Ltd:The Cataplasm
JPS58184533U (ja) * 1982-05-14 1983-12-08 ライオン株式会社 湿布薬

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56103112A (en) * 1980-01-18 1981-08-18 Nippon Synthetic Chem Ind Co Ltd:The Cataplasm
JPS58184533U (ja) * 1982-05-14 1983-12-08 ライオン株式会社 湿布薬

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997045104A1 (fr) * 1996-05-31 1997-12-04 Fuji Yakuhin Kogyo Kabushiki Kaisha Fibre ayant une capacite elevee d'absorption de l'eau et contenant de l'iode

Also Published As

Publication number Publication date
JPH05246841A (ja) 1993-09-24

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