WO1994001097A1 - Composition pour application bucale, contenant un derive de polyprenyle comme ingredient actif - Google Patents

Composition pour application bucale, contenant un derive de polyprenyle comme ingredient actif Download PDF

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Publication number
WO1994001097A1
WO1994001097A1 PCT/JP1993/000884 JP9300884W WO9401097A1 WO 1994001097 A1 WO1994001097 A1 WO 1994001097A1 JP 9300884 W JP9300884 W JP 9300884W WO 9401097 A1 WO9401097 A1 WO 9401097A1
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WO
WIPO (PCT)
Prior art keywords
active ingredient
derivative
compound
group
oral composition
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/JP1993/000884
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English (en)
Japanese (ja)
Inventor
Satoshi Shizukuishi
Kiyomi Teramoto
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.)
Sankyo Co Ltd
Original Assignee
Sankyo Co Ltd
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 Sankyo Co Ltd filed Critical Sankyo Co Ltd
Priority to AU43579/93A priority Critical patent/AU4357993A/en
Publication of WO1994001097A1 publication Critical patent/WO1994001097A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/08—Ethers or acetals acyclic, e.g. paraformaldehyde
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group

Definitions

  • the present invention relates to an oral composition
  • an oral composition comprising a polyprenyl derivative as an active ingredient, which has a prophylactic and therapeutic effect on periodontal disease.
  • periodontal disease is one of the major diseases in the dental field, and its prevention and treatment are important issues in oral hygiene.
  • the present inventors have studied the pharmacological action of a series of polyprenyl derivatives in the dental field over the years, and as a result, it has been found that certain polybrenyl derivatives increase hemoglobin oxygen saturation of gingiva and reduce the amount of genius xyhemoglobin.
  • the present invention has been found to be useful as an oral product having an effect of preventing and treating periodontal disease since it has reduced toxicity and less toxicity, and has completed the present invention.
  • polyprenyl derivatives of the present invention have been known to force s' having antiulcer activity (for example, JP 5 2-
  • the polybrenyl derivative which is the active ingredient of the present invention has the general formula
  • R 1 and R 2 are the same or different and each represent a hydrogen atom, a d-C 4 alkyl group, a C 2 —C aliphatic acyl group, a C 7 -Cn aromatic acyl group or a C 8 -C 12 aromatic aliphatic acyl group And n represents ⁇ to 2.
  • Ci -C 4 alkyl groups include methyl, Echiru, propyl, isopropyl, heptyl, s EC- heptyl, be a isobutyl group, preferably a d -C 2 Al kill groups, particularly preferred, It is a methyl group.
  • the C 2 —C 12 aliphatic acryl group may have a double bond, for example, acetyl, propionyl, butyryl, valeryl, isovaleryl, cabroyl, heptanyl, lactanoyl, nonanoyl, decanoyl, lauroyl, acryloyl, metaacryloyl , Crotomeyl, 3-butemyl, preferably C 2 -C 6 aliphatic acetyl, and particularly preferably acetyl.
  • the Cr-aromatic acyl group may be, for example, a benzoyl or naphthoyl group, preferably a benzoyl group.
  • the aromatic ring may have a substituent on the aromatic ring, for example, the above-mentioned -C 4 alkyl group, methoxy, ethoxy, Epoxy, Isopurobokishi, d -C 4 alkoxy or fluorine, such as butoxy ', chlorine, bromine, a halogen atom such as iodine to obtain, preferably,. Methyl, main Bokuki shea, fluorine, chlorine.
  • Cs one C 12 araliphatic Ashiru group may have a double bond, for example, phenylene Ruasechiru, full We sulfonyl propionyl, Fuwenirubuchiriru, Fuenirubareriru, Na Fuchiruasechiru be a cinnamoyl group, preferably, Hue Nilacetyl and a cinnamoyl group, particularly preferably a cinnamoyl group.
  • the aromatic ring may have a substituent, which is the same as that of the above-mentioned aromatic acyl group.
  • R 1 and R 2 are the same and are a hydrogen atom, a methyl group, a C 2 -C 12 aliphatic acyl group, a benzoyl group or a cinnamoyl group;
  • R 1 and R 2 are the same and are a hydrogen atom or a C 2 -C 6 aliphatic acyl group
  • R 1 and R 2 are the same and are a hydrogen atom or an acetyl group
  • R 1 and R 2 force compounds that are hydrogen atoms
  • Suitable compounds in the general formula (I) can be specifically exemplified in Table 1 below.
  • the polyprenyl derivative having the general formula (I), which is an active ingredient of the present invention can be easily produced by a known method, which is a known compound (for example, see
  • the oral &] products containing the polybrenyl derivative of the present invention as an active ingredient increase the hemoglobin oxygen saturation of gingiva, decrease the amount of teoxyhemoglobin, and have low toxicity. It is extremely useful as a prophylactic and therapeutic agent. [Industrial applicability]
  • the compound (I) When used as a prophylactic or therapeutic agent for periodontal disease, it may be used as appropriate with an abrasive (eg, dibasic calcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, silica, silica alumina, Aluminum oxyacid, aluminum hydroxide, resin, etc.), binder (for example, carboxymethylcellulose, hydroxyethyl cellulose, power lagenan, gum arabic, polyvinyl alcohol, sodium alginate, bentonite, etc.), wetting agent (Eg, polyethylene glycol, sorbitol, glycerin, propylene glycol, etc.), foaming agents (eg, sodium lauryl sulfate, sodium dodecylbenzenesulfonate, sodium laurylsulfoacetate, sucrose stearate, ash) Lusarcosine sodium, etc.), fragrances (eg, peppermint, spearmint, 1-menthol
  • Dentifrice such as toothpaste, powder toothpaste, water toothpaste, pasta agent, coating agent, mouthwash, It is used in the form of an oral composition such as a troche, chewing gum and the like (preferably a dentifrice and a liniment).
  • lysozyme chloride dextranase, lytic enzyme, mucinase, chlorhexidine, sorbic acid, alexidine, hinokitiol, cetyl pyridium chloride, alkyl glycine, alkyl diaminoethyl glycine salt , Allantoin, aminocaproic acid, tranexamic acid, azulene, vitamin E, sodium monoflurophosphate, sodium fluoride, stannous fluoride, water-soluble primary or secondary phosphate, quaternary ammonium salt, Sodium chloride and the like can also be blended.
  • the amount of the polyprenyl derivative contained in these preparations is 0.001 to 30% by weight (preferably 0.005 to 10% by weight, particularly preferably 0.01 to 2% by weight).
  • FIG. 1 shows the time course of hemoglobin oxygen saturation for the compound of Compound No. 12.
  • FIG. 2 shows the time-dependent change in the amount of deoxyhemoglobin for the compound of Compound No. 12.
  • the subjects consisted of eight subjects (five males, three females, average age 22.4 years), and the labial side of the middle and lateral incisors between the upper and lower jaw and left and right, and between the lateral incisors and canines. Gingiva was included in the study.
  • the average gingival index of the target site was 1.05
  • the average plaque index was 1.26
  • the average depth of the periodontal bottle was 2.33nun.
  • Evaluation of gingival microcirculation was performed using tissue reflectance spectrum analysis. That is, the reflection spectrum of the gingiva was measured using a tissue spectrum analyzer (TS-200, manufactured by Sumitomo Electric Industries, Ltd.), and the total hemoglobin amount, hemoglobin oxygen saturation, and xyhemoglobin amount were determined by spectrum analysis. And the amount of oxyhemoglobin is calculated and used as an indicator of blood flow and oxygen supply and demand dynamics. Before, 1, 5, 10, 20, and 30 minutes after application of each sample, measure the reflection spectra of five gingiva samples Then, the total hemoglobin amount, hemoglobin oxygen saturation, the amount of hemoglobin and the amount of hemoglobin were calculated by spectral analysis, and the average value was used as the representative value of the site. The results are shown in Table 2 using the values before application as 10Q and using the relative values. Prior to the experiment, the absorption spectrum of each drug used was measured by transmission spectroscopy, and it was confirmed that these did not affect the reflection spectrum analysis.
  • TS-200 tissue spectrum analyzer
  • the following components were mixed to produce a toothpaste according to a conventional method.
  • the following components were mixed to produce a gingival coating according to a conventional method.

Landscapes

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

Abstract

L'invention concerne une composition pour application bucale, contenant un dérivé de polyprényle répondant à la formule générale (I) comme ingrédient actif. Dans ladite formule (I), R1 et R2 peuvent être identiques ou différents et représentent chacun hydrogène, alkyle C¿1?-C4, acyle aliphatique C2-C12, acyle aromatique C7-C11 où acyle araliphatique C8-C12, et n peut valoir de 0 à 2. Cette composition est utilisée pour augmenter le degré de la saturation en oxygène de l'hémoglobine de la gencive et réduire la quantité de désoxyhémoglobine, ainsi que pour prévenir ou traiter les maladies parodontales.
PCT/JP1993/000884 1992-07-01 1993-06-29 Composition pour application bucale, contenant un derive de polyprenyle comme ingredient actif Ceased WO1994001097A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU43579/93A AU4357993A (en) 1992-07-01 1993-06-29 Composition for buccal application containing polyprenyl derivative as active ingredient

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP17410092 1992-07-01
JP4/174100 1992-07-01

Publications (1)

Publication Number Publication Date
WO1994001097A1 true WO1994001097A1 (fr) 1994-01-20

Family

ID=15972651

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1993/000884 Ceased WO1994001097A1 (fr) 1992-07-01 1993-06-29 Composition pour application bucale, contenant un derive de polyprenyle comme ingredient actif

Country Status (2)

Country Link
AU (1) AU4357993A (fr)
WO (1) WO1994001097A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5262213A (en) * 1975-11-18 1977-05-23 Sankyo Co Ltd Polypluenyl derivatives
JPS6061524A (ja) * 1983-08-31 1985-04-09 ジ　アツプジヨン　カンパニ− 歯槽骨吸収の治療
JPH0459736A (ja) * 1990-06-26 1992-02-26 Lion Corp 口腔用組成物
JPH0477424A (ja) * 1990-07-18 1992-03-11 Lotte Co Ltd 抗歯周病剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5262213A (en) * 1975-11-18 1977-05-23 Sankyo Co Ltd Polypluenyl derivatives
JPS6061524A (ja) * 1983-08-31 1985-04-09 ジ　アツプジヨン　カンパニ− 歯槽骨吸収の治療
JPH0459736A (ja) * 1990-06-26 1992-02-26 Lion Corp 口腔用組成物
JPH0477424A (ja) * 1990-07-18 1992-03-11 Lotte Co Ltd 抗歯周病剤

Also Published As

Publication number Publication date
AU4357993A (en) 1994-01-31

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