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WO2004069261A1 - Procede de production d'une preparation contre le virus de l'herpes a usage externe - Google Patents

Procede de production d'une preparation contre le virus de l'herpes a usage externe Download PDF

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Publication number
WO2004069261A1
WO2004069261A1 PCT/JP2003/001047 JP0301047W WO2004069261A1 WO 2004069261 A1 WO2004069261 A1 WO 2004069261A1 JP 0301047 W JP0301047 W JP 0301047W WO 2004069261 A1 WO2004069261 A1 WO 2004069261A1
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WO
WIPO (PCT)
Prior art keywords
preparation
virus
acid
alcohol
sorivudine
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.)
Ceased
Application number
PCT/JP2003/001047
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English (en)
Japanese (ja)
Inventor
Masaichi Yamamoto
Haruhiko Machida
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Arigen Pharmaceuticals Inc
Original Assignee
Arigen Pharmaceuticals Inc
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 Arigen Pharmaceuticals Inc filed Critical Arigen Pharmaceuticals Inc
Priority to JP2004567854A priority Critical patent/JPWO2004069261A1/ja
Priority to PCT/JP2003/001047 priority patent/WO2004069261A1/fr
Publication of WO2004069261A1 publication Critical patent/WO2004069261A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/09—Pyrimidine radicals with arabinosyl as the saccharide radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses

Definitions

  • the present invention relates to a method for producing an external preparation for anti-herpes virus which exhibits strong anti-herpes virus action and is excellent in safety and stability.
  • Herpes virus is a DNA virus that has a double-stranded DNA genome, an icosahedral capsid, and an envelope derived from the host cell nuclear envelope.
  • Herpesviruses There are six typical herpesviruses that are pathogenic to humans: 1 simple herpesvirus 1 (HSV-1) 2 simple herpesvirus 2 (HSV-2) 3 varicella Herpes zoster virus (VZV) 3 Ebstein-Barr virus (EBV) 4 Cytomegalovirus (CMV) 5 Human virus 6 type.
  • Herpesviridae virus infects the human body first, then latently infects. When the host person becomes immunocompromised, it is reactivated and becomes morbid (relapse).
  • the primary infection is an exogenous infection from the host that has the virus and the environment (ice-infection-vertical infection), and the recurrent disease is an endogenous infection from within itself.
  • the varicella-zoster virus hides in ganglia and is reactivated when the host's immune system is compromised, causing painful rashes and herpes (shingles) along the ganglia.
  • Herpes infections tend to increase with aging, stress, and an increase in the number of AIDS patients, and are a major social problem.
  • anti-herpes virus drugs Few drugs have been put into practical use as anti-herpes virus drugs, and at present, acyclovir, vidarabine, ganciclovir, etc. are used as anti-herpes virus drugs.
  • Japanese Patent Publication No. 57-48160 describes that 5-[(E) -2-halogenovinyl) arabinofuranosylperacyl has antiviral activity, and among them, 1--D-arabinofuranosyl- 5-[(E) -2-bromovul] peracyl (generic name: soribudine) has excellent antiviral activity, especially against HSV-1, EBV and VZV. This was launched in Japan in 1993 under the brand name Teenville Tablets, but since it was developed as an oral drug, patients who co-administered with a fluorouracil-based anticancer drug died due to side effects due to the interaction. It was a big problem.
  • BV D bromobulperacyl
  • Sorivudine is known to show a very strong anti-herpesvirus effect in the in Vro test compared to other anti-herpesvirus agents.
  • application to the skin suppressed the skin symptoms caused by inoculation of herpes virus type I (Antiviral Research, 21, 47-57, 1993).
  • 5-[(E) -2-halogenovinyl] arabinofuranosylperacyl, which contains soribudine, is hardly soluble. Therefore, ointment is applied in a usual manner using a conventional base used in external preparations. It has been difficult to produce stable external preparations such as olive oil and juru. Therefore, no consideration has been given as to whether these compounds can be used as effective and safe external preparations, and their interaction with fluorouracil drugs. Disclosure of the invention
  • An object of the present invention is to provide 5-[(E) -2-halogenovinyl) arapinofuranosyl-dilacil containing sorivudine, while maintaining a strong anti-herpesvirus effect, and interacting with a fluorouracil-based anticancer agent.
  • An object of the present invention is to provide a method for producing a topical virus virus preparation that is highly safe and does not exhibit side effects.
  • BVD bromovinylperacyl
  • the inventor of the present invention has found a method for producing an external preparation for using sorivudine or the like as an external preparation as a result of intensive studies, and the external preparation obtained in this way is used for herpes virus, particularly varicella-zoster virus (VZV).
  • VZV varicella-zoster virus
  • the present inventors have found that the present invention can effectively suppress the growth of BVD, prevent the production and reabsorption of BVD in the intestinal tract, and avoid the interaction with a fluorouracil-based anticancer agent.
  • the present invention relates to a method for producing a preparation for external use of anti-herpesvirus comprising 5-[(E) -2-halogenovinyl) arabinofuranosylperacyl represented by the following general formula (I) as an active ingredient.
  • the present invention relates to the above-mentioned production method, characterized by comprising heating under reduced pressure in any one or more of the steps for blending into the base.
  • X represents a halogen atom
  • X is preferably a bromine atom or a chlorine atom.
  • the present invention also relates to an external preparation for anti-herpes virus containing 5-[(E) -2-halogenovinyl) arabinofuranosylperacyl obtained by the above-mentioned production method as an active ingredient.
  • the 5-[(E) -2-halogenovinyl) arabinofuranosylperacyl represented by the general formula (I) used in the method of the present invention for producing an external preparation for anti-herpes virus The compound described in Japanese Patent Publication No. 57-48160 (US Pat. No. 4,386,076) has a potent anti-herpesvirus action, particularly a selective inhibitory action against VZV. In addition, the growth inhibitory effect on cells not infected with the virus is extremely low.
  • This compound can be synthesized by a known method, for example, the method described in the above publication, or a method analogous thereto.
  • R in the general formula (I) represents a halogen atom such as chlorine, bromine, iodine, or fluorine, and a compound in which R is a bromine atom.
  • the compound of the above general formula (I) is made into an external preparation together with a suitable pharmaceutically acceptable base.
  • a suitable pharmaceutically acceptable base any base commonly used in the manufacture of external preparations can be used.However, a base with less irritation or pain during application is selected for use in patients with abnormal skin such as shingles. I do.
  • the form of the preparation may be any form such as an ointment, cream, jule, cataplasm, plaster, patch and the like.
  • the active ingredient 5-[(E) -2-octogenobul) arabinofuranosyl peracyl may be added to one or more of the steps for blending in the base. And heating under reduced pressure.
  • an oil base or emulsion base may be used as a base.
  • the above-mentioned active ingredient or active ingredient is mixed with a base such as propylene glycol and the like under a reduced pressure by heating, stirring and mixing with an oily base.
  • a base such as propylene glycol and the like
  • the above active ingredient dissolved in a base such as propylene glycol under heating under reduced pressure is heated under reduced pressure in a previously prepared emulsion base. Added.
  • a joule agent is prepared by dissolving a joule base in water, adding a hydrophilic organic solvent, and gradually dissolving the active ingredient in a base such as dipropylene glycol under heating under reduced pressure. It can be manufactured by adding.
  • plasters, patches, and cataplasms plasters containing active ingredients obtained by a method similar to the above method are spread on a support such as a nonwoven fabric or woven fabric, and cut into appropriate sizes. Can be manufactured.
  • oils and fats examples include oils and fats, waxes, hydrocarbons, fatty acids, alcohols, alkyl glyceryl ethers, esters, silicone oils, fluorine oils, and polyhydric alcohols.
  • Vegetable oils include olive oil, safflower oil, persic oil, cucumber oil, wheat germ oil, rice bran oil, rice germ oil, evening primrose oil, high oleic sunflower oil, macadamia nut oil, meadow home oil, and the like.
  • Animal oils include tallow, hardened oil, and egg yolk fatty oil.
  • Waxes are mainly composed of esters of higher fatty acids and higher alcohols (wax esters).
  • the carbon number of the ester is widely used as C12-C34.
  • Animal systems include lanolin, whale wax, beeswax, shellac wax, and liquid orange roughy oils, and plant systems include carnaupa wax, candelillaro ' ⁇ , and liquid jojoba oil.
  • hydrocarbon examples include chain hydrocarbons, and liquid paraffins, which are mixtures of various hydrocarbons, branched paraffins, solid paraffins, and serine.
  • Fatty acids include natural and synthetic fatty acids, and include, for example, raperic acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, 12-hydroxystearic acid, pendecylic acid, and the like.
  • Alcohols include, for example, higher alcohols of about C8 to C32, i.e., cabrilyl alcohol, capryl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, peryl alcohol, behyl alcohol, seryl alcohol, Laxeryl alcohol and the like. Animal and plant sterols can also be used.
  • alkyl glyceryl ether examples include batyl alcohol, chimyl alcohol, seraky alcohol, and isostearyl glyceryl ether.
  • Esters are compounds obtained by the dehydration reaction of fatty acids and alcohols.
  • Esters of linear fatty acids with lower alcohols include ethyl oleate, isopropyl myristate, butyl stearate, etc.
  • Esters of linear fatty acids with linear higher alcohols are cetyl palmitate and myristin. Acid myristyl and the like.
  • Esters of linear fatty acids and higher branched alcohols include octyldodecyl myristate and octyldodecyl oleate.
  • Esters of linear fatty acids and polyhydric alcohols include triglycerides of medium chain fatty acids.
  • Examples of the ester of a branched fatty acid and a lower alcohol include isopropyl isostearate and butyl isostearate.
  • Examples of the ester of a branched fatty acid and a higher linear alcohol include cetyl 2-ethylhexanoate and 2-ethylhexanoic acid. Stearyl is mentioned.
  • Examples of the ester of a branched fatty acid and a straight-chain higher alcohol, and the ester of a branched fatty acid and a branched higher alcohol include isosetyl isostearate and octyldodecyl dimethyloctanoate.
  • examples of the ester of hydroxycarboxylic acid and alcohol include myristyl lactate, trioctyldodecyl citrate, diisostearyl phosphate, and the like.
  • silicone oil examples include dimethyl silicone oil, methylphenyl silicone oil, cyclic dimethyl silicone oil, methyl hydridone silicone oil and modified silicone oil, and examples of fluorine oil include perfluoropolyether .
  • polyhydric alcohols examples include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol. , 1,3-butylene glycol and the like.
  • Emulsifiable bases that can be used in the present invention include 0 / W bases, W / 0 bases and suspending bases.
  • the 0 / W base components such as lanolin, propylene glycol, stearyl alcohol, petrolatum, silicone oil, liquid paraffin, glyceryl monostearate, etc. in the aqueous phase in the presence or absence of a surfactant
  • the W / 0 base is prepared by emulsifying and dispersing components such as serine, higher fatty acid alcohol, and liquid paraffin with water in the presence of a nonionic surfactant. Is mentioned.
  • fatty acid monoglyceride Polyoxyethylene nonionic surfactants such as polyhydric alcohol esters such as rubitan fatty acid esters, sucrose and polyglycerin fatty acid esters, polyoxyethylene derivatives of aliphatic alcohols, and polyoxyethylene derivatives of fatty acids; Can be used.
  • the suspendable base include an aqueous base formed by adding glycerin, carboxymethylcellulose, carboxylic acid polymer, water and the like to form a gel.
  • a support such as nonwoven fabric, pectin, polyacrylic acid or a salt thereof, polybutyl alcohol, polybutylpyrrolidone-butyl acetate copolymer ', polyethylene oxide, carboxymethylcellulose, hydroxypropyl Bases such as cellulose, methylcellulose, alginate, xanthan gum, tragacanth gum, methylbutyl ether, and maleic anhydride copolymer can be used.
  • the adhesive include synthetic polymer compounds such as carboxyvinyl polymer and the like and natural polymer compounds such as gum arabic and xanthan rubber.
  • the surfactant include polysorbate 80 and sorbitan sesquioleate.
  • citric acid, tartaric acid or the like can be used, and as the curing agent, a polyvalent metal compound such as zinc oxide or aluminum hydroxide can be used.
  • antioxidants can be used to enhance the stability in the formulation. Specifically, vitamin E, nordihydroguaiarenic acid, butylhydroxyanisole (BHA), dibutylhydroxytoluene (BHT), propyl gallate, erythorbic acid, sodium erisorbate, ascorbyl palmitate, and ascorbyl stearate And the like. Further, preservatives such as paraoxybenzoic acid, methylparaben, ethylparaben, and propylparaben, and perfumes may be added.
  • This product is used for patients infected with herpes simplex virus herpes zoster virus, etc., it is possible to prevent the skin from drying out, especially by adding a moisturizer.
  • Polyhydric alcohol for moisturizer Sugars, biopolymers, etc. can be used.
  • polyhydric alcohols include glycerin propylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, isoprene glycol, P0E methyl glucoside, and the like.
  • saccharide examples include trehalose, pullulan, and maltose.
  • examples of the biopolymer include sodium hyaluronate, sodium chondroitin sulfate, collagen, and elastin.Others include amino acids, sodium lactate, and sodium pyrrolidone carbonate. Examples include lium and urea.
  • aminocarboxylic acid, glycyrrhizic acid, monoglycyrrhetinic acid, lysozyme chloride, hydrocortisone and the like may be blended.
  • the compound of the above-mentioned general formula (I) having a strong anti-Herwirs virus action which is also proved by ⁇ vitro, is used as an active ingredient, and as shown in the following examples, in V 1 vo kinetics "Experiment 1" can also provide an anti-herpesvirus external preparation that can exert an anti-virus virus action. It is possible to avoid the interaction with fluorouracil-based drugs, which is a problem in the above, and there is no skin toxicity, therefore, it can be used as a safe and effective therapeutic agent for herpes virus infection, especially Its strong selective inhibitory effect on varicella-zoster virus allows effective treatment of herpes zoster.
  • the dose of the external preparation obtained according to the present invention varies depending on age, disease state, sex, days after onset, etc., but preferably 1 to 100 mg / kg per day as the compound of the general formula (I) as an active ingredient. Weight.
  • a composition containing 0.1 to 10%, particularly 0.5 to 5%, of the compound of the formula (I) is applied to a lesion on the skin of a patient once to several times a day. Is preferred.
  • FIG. 1 is a diagram showing the results of tests on the antiviral effect of the external preparation obtained by the present invention using a mouse skin infection model.
  • BEST MODE FOR CARRYING OUT THE INVENTION will be described more specifically with reference to examples, but the present invention is not limited thereto.
  • a solution prepared by dissolving 300 g of 5-chlorovinylara U and 1.7 kg of propylene glycol in a preliminarily prepared emulsion as described above in place of sorivudine as the main component while heating at 75 ° C under reduced pressure at 75 ° C. was gradually added in the same manner as above to obtain 10 kg of a 5-chlorovinylara U 3% cream preparation (Formulation No. 4).
  • Example 4 Propylene glycol lkg 100 g of sorivudine and 50 g of polysorbate 80 are mixed by stirring under reduced pressure so as to be uniform. Separately, 1.5 g of glycerin, 500 g of titanium dioxide, and 500 g of sodium polyacrylate are mixed, and 6.15 kg of purified water and 200 g of citric acid are added to this solution, and the mixture is heated and dissolved at 50 to 55 ° C under reduced pressure to obtain a uniform solution. Solution. The solution prepared above is gradually added to this solution, and the solution is heated and dissolved at 50 to 55 ° C. under reduced pressure to obtain a sorivudine-containing plaster having a pH of 5. Next, this was spread on a piece of cloth, and the plaster surface was covered with a storage film and cut into a predetermined size to obtain a poultice containing 1% sorivudine (formulation No. 7).
  • Example 1 Using the cream obtained in Example 1 in a mouse skin infection model of HSV-1 (Uichi et al., Antiviral Research, 21, 47, 1993), the appropriate efficacious concentration of this formulation was determined as follows. Was observed.
  • mice Male Balb / c mice were tested.The right half of the body was shaved under Nembutal anesthesia. did. HSV-1 WT-51 strain was applied to the abraded area. The drug was applied four times a day for 7 days using a cotton swab 16 hours after virus inoculation, including the site of virus inoculation, to the area where a band-like lesion might appear. The mice were observed for life and death for 20 days. As a positive control, Zovirax (trade name of acyclovir) 5% ointment was used (NO. 8). For placebo, a formulation (NO. 9) was prepared from the formulation of Example 1 except for sorivudine.
  • Sorivudine 3% cream formulation obtained in Example 1 and 5-Chlorovinylara U 3% cream formulation (NO. 4), sorivudine 3% ointment (NO. 5), and the sorivudine 3% gel agent (NO. 6) obtained in Example 3 and the poultice agent (NO. 7) obtained in Example 4 as a fluorouracil-based drug, 5-FU.
  • the presence or absence of interaction with was observed.
  • female rats of the Wsitter series were preliminarily reared for one week, then shaved from the scapula to the lumbar region under anesthesia, and the preparations were applied to the portions three times a day for 7 days.
  • the red blood cell count and white blood cell count indicate the measured values 7 days after administration.
  • the manufacturing method of the anti-herpes virus external preparation of the present invention it is possible to obtain an external preparation having a high anti-herpes virus activity, and being safe and excellent in stability.
  • This topical formulation while maintaining excellent anti-herpes' virus activity, can avoid the interaction of sorivudine with fluorouracils, which was a problem with oral drugs, especially in the form of varicella. Effective for the treatment of herpes.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de production d'une préparation contre le virus de l'herpès à usage externe, ladite préparation contenant comme ingrédient actif 5-[(E)-2-halogènovinyl]arabinofuranosyluracile représenté par la formule générale suivante (I). Ledit procédé est caractérisé en ce qu'à n'importe laquelle des étapes d'incorporation de l'ingrédient actif dans une base, le chauffage est réalisé à basse pression. Dans ladite formule (I), X représente l'halogène. Ce procédé permet d'obtenir une préparation à usage externe qui est une préparation contre le virus de l'herpès possédant une activité élevée de lutte contre le virus de l'herpès et qui, en dépit de cela, présente une innocuité et une stabilité excellentes.
PCT/JP2003/001047 2003-02-03 2003-02-03 Procede de production d'une preparation contre le virus de l'herpes a usage externe Ceased WO2004069261A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2004567854A JPWO2004069261A1 (ja) 2003-02-03 2003-02-03 抗ヘルペスウイルス外用製剤の製造方法
PCT/JP2003/001047 WO2004069261A1 (fr) 2003-02-03 2003-02-03 Procede de production d'une preparation contre le virus de l'herpes a usage externe

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Application Number Priority Date Filing Date Title
PCT/JP2003/001047 WO2004069261A1 (fr) 2003-02-03 2003-02-03 Procede de production d'une preparation contre le virus de l'herpes a usage externe

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8361446B2 (en) 2005-04-28 2013-01-29 Basf Se Use of benzotriazole derivatives for photostabilisation
JP2016518424A (ja) * 2013-05-14 2016-06-23 ナイェファルム・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＮａｊｏＰｈａｒｍ ＧｍｂＨ ヘルペス処置のための薬剤と方法
JPWO2021149827A1 (fr) * 2020-01-24 2021-07-29

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09143096A (ja) * 1995-11-27 1997-06-03 Pola Chem Ind Inc ウィルス疾患用医薬組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09143096A (ja) * 1995-11-27 1997-06-03 Pola Chem Ind Inc ウィルス疾患用医薬組成物

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 119, no. 173633, Columbus, Ohio, US; XP002903706 *
CHEMICAL ABSTRACTS, vol. 96, no. 62635, Columbus, Ohio, US; XP002903705 *
SADANOBU OKANO: "Shin.Yakuzaigaku Soron", 10 April 1987, NANKODO CO,LTD., pages: 88, XP002903707 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8361446B2 (en) 2005-04-28 2013-01-29 Basf Se Use of benzotriazole derivatives for photostabilisation
JP2016518424A (ja) * 2013-05-14 2016-06-23 ナイェファルム・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＮａｊｏＰｈａｒｍ ＧｍｂＨ ヘルペス処置のための薬剤と方法
JPWO2021149827A1 (fr) * 2020-01-24 2021-07-29
WO2021149827A1 (fr) * 2020-01-24 2021-07-29 ノーベルファーマ株式会社 Préparation externe contenant de la rapamycine
JP7755854B2 (ja) 2020-01-24 2025-10-17 ノーベルファーマ株式会社 ラパマイシン含有外用剤

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