[go: up one dir, main page]

WO2016013551A1 - Composition topique - Google Patents

Composition topique Download PDF

Info

Publication number
WO2016013551A1
WO2016013551A1 PCT/JP2015/070741 JP2015070741W WO2016013551A1 WO 2016013551 A1 WO2016013551 A1 WO 2016013551A1 JP 2015070741 W JP2015070741 W JP 2015070741W WO 2016013551 A1 WO2016013551 A1 WO 2016013551A1
Authority
WO
WIPO (PCT)
Prior art keywords
component
weight
therapeutic agent
acid
skin
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/JP2015/070741
Other languages
English (en)
Japanese (ja)
Inventor
友美 長谷川
寛和 金本
孝広 中田
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.)
Kobayashi Pharmaceutical Co Ltd
Original Assignee
Kobayashi Pharmaceutical 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 Kobayashi Pharmaceutical Co Ltd filed Critical Kobayashi Pharmaceutical Co Ltd
Priority to HK17105154.2A priority Critical patent/HK1231396B/zh
Priority to CN201580040294.3A priority patent/CN106659713B/zh
Publication of WO2016013551A1 publication Critical patent/WO2016013551A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a prophylactic or therapeutic agent for hypertrophic scar and / or keloid.
  • the present invention also relates to a formation inhibitor that suppresses the formation of granulation tissue.
  • the present invention relates to a composition for external use which is excellent in the effect of preventing or treating hypertrophic scar and / or keloid and the effect of suppressing granulation formation.
  • Hypertrophic scars and keloids are red, such as bulges (bumps), redness, tightness, and lump, due to excessive tissue repair after excessive wound granulation and extracellular matrix accumulation after wounding.
  • Abnormal skin tissue with elevated lesions While hypertrophic scars are difficult to spread beyond the wound area and are characterized by fading of color tone and a decrease in swell over time, keloids can spread lesions beyond the wound area. There is a feature that it is difficult to recognize the fading of the color tone or the decrease of the climax with the passage of time.
  • both hypertrophic scars and keloids are common in that they are raised lesions with reddening of the skin caused by excessive proliferation of granulation cells and accumulation of extracellular matrix.
  • suppression of excessive proliferation of granulation cells, suppression of excessive accumulation of extracellular matrix, anti-inflammation of lesions, etc. are effective.
  • steroids and heparin-like substances have been used conventionally.
  • the steroid agent is excellent in therapeutic effect itself, it may cause side effects such as skin atrophy, capillary vasodilation, and infectivity, and attention is required for the amount used and the period of use.
  • heparin-like substances are widely used for the treatment of hypertrophic scars and keloids, but their therapeutic effects are not fully satisfactory.
  • heparin-like substances do not have side effects like steroids, if a pharmaceutical formulation that can improve the prevention or treatment effect of hypertrophic scars and / or keloids by heparin-like substances can be developed, hypertrophic scars and / or Or it is expected to bring the gospel to patients suffering from keloids.
  • Patent Document 1 discloses that by using a heparin-like substance and betaines in combination, an excellent therapeutic effect can be achieved for rough skin associated with dry skin diseases and inflammatory skin diseases.
  • Patent Document 2 discloses that a combination of a heparin-like substance and a non-steroidal anti-inflammatory agent can provide an excellent therapeutic effect for dry skin diseases and inflammatory skin diseases.
  • Patent Document 3 discloses that normal differentiation of epidermal keratinocytes into horny cells can be promoted by combining a heparin-like substance, allantoin or a derivative thereof, and pantothenic acid or a derivative thereof.
  • An object of the present invention is to provide a pharmaceutical formulation that can improve the effect of preventing or treating hypertrophic scars and / or keloids with a heparin-like substance, or the granulation tissue formation-inhibiting action with a heparin-like substance.
  • the present inventor made extensive studies to solve the above problems, and combined use of (A) heparin-like substance and (B) allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and / or salts thereof.
  • Item 1 (A) a heparin-like substance, and (B) at least one selected from the group consisting of allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof, and hypertrophic scar and An agent for preventing or treating keloid.
  • Item 2. Item 2. The prophylactic or therapeutic agent according to Item 1, comprising at least one selected from the group consisting of (B-1) allantoin and derivatives thereof as the component (B).
  • the component (B) at least one selected from the group consisting of (B-1) allantoin and derivatives thereof, and (B-2) a group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof Item 3.
  • the preventive or therapeutic agent according to Item 1 or 2 comprising at least one selected from the group consisting of: Item 4.
  • Item 5. Item 5.
  • the prevention or treatment according to Item 3 or 4 comprising 5 to 10,000 parts by weight of the component (B-1) and 5 to 10,000 parts by weight of the component (B-2) per 100 parts by weight of the component (A).
  • Agent. Item 6.
  • Item 6. The preventive or therapeutic agent according to any one of Items 1 to 5, comprising 0.01 to 5% by weight of the component (A).
  • Item 7. Item 7.
  • Item 8. Item 8.
  • the preventive or therapeutic agent according to any one of claims 1 to 8, which is used for improving the lump of the skin after a wound or burn, or improving the firmness of the skin after a wound or burn.
  • Item 10 Granulation tissue formation comprising (A) a heparin-like substance and (B) at least one selected from the group consisting of allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof Inhibitor.
  • Item 11 Item 11.
  • the granulation tissue formation inhibitor according to Item 10 containing at least one selected from the group consisting of (B-1) allantoin and derivatives thereof as the component (B).
  • the component (B) at least one selected from the group consisting of (B-1) allantoin and derivatives thereof, and (B-2) a group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof Item 12.
  • Item 13 The granulation tissue formation inhibitor according to any one of Items 10 to 12, wherein the total amount of the component (B) is 10 to 20000 parts by weight per 100 parts by weight of the component (A).
  • Item 15. Item 15.
  • Item 16. Item 16.
  • Agent. Item 18.
  • the granulation tissue formation inhibitor according to any one of Items 10 to 17, which is used for improving the lump of the skin after scratches or burns or the firmness of the skin after scratches or burns.
  • Item 19 (A) at least one selected from the group consisting of heparin analogues, (B-1) allantoin and derivatives thereof, and (B-2) a group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.
  • the composition for external use characterized by containing at least 1 sort (s) selected from these.
  • Item 20 Item 20.
  • the topical composition according to Item 19 comprising 5 to 10,000 parts by weight of the component (B-1) and 5 to 10,000 parts by weight of the component (B-2) per 100 parts by weight of the component (A).
  • Item 21. The external composition according to Item 19 or 20, comprising 0.01 to 5% by weight of the component (A).
  • Item 22. The composition for external use according to any one of Items 19 to 21, comprising 0.01 to 5% by weight of the component (B-1).
  • Item 23 Item 23.
  • Item 24 Item 24.
  • the prophylactic or therapeutic effect of hypertrophic scars and / or keloids can be significantly improved as compared with the case where a heparin-like substance is used alone.
  • a heparin-like substance is used alone.
  • skin diseases and skin symptoms caused by excessive formation of granulation tissue such as skin swell, redness, tension, and lump can be effectively prevented. Can be prevented or treated.
  • Test example 2 the result of having measured the color of the affected part and the healthy skin with the spectrocolorimeter about four test subjects in the group which applied the cream of Example 4 is shown.
  • Test example 2 the result of having measured the color of the affected part and the healthy skin with the spectrocolorimeter about four test subjects in the group which applied the cream agent of the comparative example 2 is shown.
  • the preventive or therapeutic agent of the present invention is selected from the group consisting of heparin-like substances (hereinafter also referred to as component (A)), allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof. At least one (hereinafter also referred to as component (B)), and is used for the prevention or treatment of hypertrophic scars and / or keloids.
  • component (A) heparin-like substances
  • component (B) At least one
  • component (B) is used for the prevention or treatment of hypertrophic scars and / or keloids.
  • the preventive or therapeutic agent of the present invention contains a heparin-like substance as component (A).
  • a heparin-like substance is a polysulfated mucopolysaccharide such as chondroitin polysulfate, and is a known drug known to have a moisturizing action, a blood flow increasing action, and the like.
  • the origin of the heparin-like substance used in the present invention is not particularly limited. For example, it is obtained by polysulfating mucopolysaccharides, tissues of edible animals (for example, tracheal cartilage such as cattle and pigs) And the like extracted from the lung including In the preventive or therapeutic agent of the present invention, as the heparin-like substance, a heparin-like substance included in the Japanese Pharmacopoeia Pharmaceutical Standards is preferably used.
  • the blending amount of the component (A) in the preventive or therapeutic agent of the present invention may be appropriately set according to the preparation form of the prophylactic or therapeutic agent, for example, 0.01 to 5% by weight, preferably 0. It is 05 to 3% by weight, more preferably 0.1 to 1% by weight.
  • the preventive or therapeutic agent of the present invention contains, as component (B), at least one selected from the group consisting of allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.
  • component (B) at least one selected from the group consisting of allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.
  • Allantoin is a compound also called 5-ureidohydantoin, and is a known drug known to have anti-inflammatory action, antipruritic action and the like.
  • the allantoin derivative is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include allantoin chlorohydroxyaluminum and allantoinhydroxyaluminum. These allantoin derivatives may be used alone or in combination of two or more.
  • Glycyrrhizic acid is a known drug known to have an anti-inflammatory action, an antiallergic action, and the like.
  • the derivative of glycyrrhizic acid is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include methyl glycyrrhizinate and stearyl glycyrrhizinate. These glycyrrhizic acid derivatives may be used alone or in combination of two or more.
  • the salt of glycyrrhizic acid and its derivative is not particularly limited as long as it is pharmacologically acceptable, and specific examples include alkali metal salts such as sodium salt, potassium salt, dipotassium salt; ammonium salt and the like. It is done. These salts of glycyrrhizic acid and its derivatives may be used alone or in combination of two or more.
  • Glycyrrhetinic acid is a known drug known to have an anti-inflammatory action, an antiallergic action, and the like.
  • the derivative of glycyrrhetinic acid is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, monoglucuronide glycyrrhetinate, and the like. These glycyrrhetinic acid derivatives may be used alone or in combination of two or more.
  • the salt of glycyrrhetinic acid and its derivative is not particularly limited as long as it is pharmacologically acceptable, and specific examples include alkali metal salts such as sodium salt and potassium salt; ammonium salt and the like. These salts of glycyrrhetinic acid and its derivatives may be used alone or in combination of two or more.
  • One type may be selected from among acid derivatives and glycyrrhetinic acid derivative salts, or two or more types may be used in combination.
  • component (B) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof (hereinafter sometimes referred to as component (B-2)) ),
  • glycyrrhizic acid, a derivative thereof, and / or a salt thereof more preferably glycyrrhizic acid, from the viewpoint of further improving the effect of preventing or treating hypertrophic scars and / or keloids.
  • / or a salt thereof more preferably dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, particularly preferably dipotassium glycyrrhizinate.
  • (B) components from the viewpoint of achieving a more prominent hypertrophic scar and / or keloid prevention or treatment effect, preferably (B-1) component, more preferably (B-1) component And a combination of components (B-2).
  • the ratio of the component (A) and the component (B) is not particularly limited, but from the viewpoint of further improving the preventive or therapeutic effect of hypertrophic scar and / or keloid (
  • the total amount of component (B) is 10 to 20000 parts by weight, preferably 30 to 7000 parts by weight, more preferably 30 to 5000 parts by weight, even more preferably 30 to 1600 parts by weight per 100 parts by weight of component A). Is 50 to 700 parts by weight.
  • the component (B-1) when used alone as the component (B), the component (B-1) is preferably 5 to 10,000 parts by weight per 100 parts by weight of the component (A). Is 50 to 2000 parts by weight, more preferably 30 to 700 parts by weight, and still more preferably 60 to 350 parts by weight.
  • the component (B-2) when used alone as the component (B), the component (B-2) is 5 to 10,000 parts by weight, preferably 50 to 5000 parts by weight per 100 parts by weight of the component (A). More preferred is 10 to 3000 parts by weight, even more preferred is 30 to 1000 parts by weight, and particularly preferred is 60 to 350 parts by weight.
  • the component (B-1) is 5 to 10,000 parts by weight per 100 parts by weight of the component (A).
  • Parts preferably 50 to 5000 parts by weight, more preferably 50 to 2000 parts by weight, still more preferably 30 to 700 parts by weight, still more preferably 60 to 350 parts by weight
  • the component (B-2) is 5 to 10,000 parts by weight.
  • 50 to 5000 parts by weight more preferably 10 to 3000 parts by weight, still more preferably 30 to 1000 parts by weight, and particularly preferably 60 to 350 parts by weight.
  • the blending amount of the component (B) in the preventive or therapeutic agent of the present invention may be appropriately set according to the preparation form of the preventive or therapeutic agent, the ratio of the component (A) and the component (B) described above, etc. Examples thereof include 0.01 to 15% by weight, preferably 0.05 to 8% by weight, and more preferably 0.1 to 5% by weight.
  • the blending amount of the component (B-1) is, for example, 0.01 to 5% by weight, preferably 0. 0.05 to 3% by weight, more preferably 0.05 to 2% by weight, and still more preferably 0.1 to 2% by weight.
  • the amount of component (B-2) is, for example, 0.01 to 10% by weight, preferably 0.05 to 5% by weight. More preferred is 0.05 to 3% by weight, still more preferred is 0.1 to 3% by weight.
  • the blending amount of the component (B-1) is, for example, 0.01 to 5% by weight, Preferably it is 0.05 to 3% by weight, more preferably 0.05 to 2% by weight, still more preferably 0.1 to 2% by weight.
  • the blending amount of component (B-2) is, for example, 0.01 to 10%. % By weight, preferably 0.05 to 5% by weight, more preferably 0.05 to 3% by weight, and still more preferably 0.1 to 3% by weight.
  • the preventive or therapeutic agent of the present invention may contain other pharmacological components as necessary in addition to the components (A) and (B).
  • pharmacological components include antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics (procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, propalacaine, meprilucaine or salts thereof, orthocaine, oxesasein, oxypolyentoxy Decane, funnel extract, percaminpase, tesit decite, etc.), anti-inflammatory agents (indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), skin protectants (collodion, castor oil, etc.), blood circulation promoting components (nonyl acid vanillylamide, nicotinic acid benzyl ester) , Capsaicin, pepper extract, etc.),
  • the base material and the additive may be contained as needed.
  • bases and additives are not particularly limited as long as they are pharmaceutically acceptable.
  • Aqueous bases such as glycol, 1,3-butylene glycol, etc .
  • oils oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.
  • Mineral oil liquid paraffin, paraffin, gelled hydrocarbon, petroleum jelly, etc.
  • waxes and waxes honey bees, carnauba wax, candelilla wax, ceresin, rice wax, microcrystalline wax, etc.
  • ester oil isopropyl myristate
  • Isopropyl adipate sebacic acid Ethyl, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate, etc.
  • fatty acid alkyl esters fatty acids (stearic acid, oleic acid, palmitic acid, behenic acid, linoleic acid, lanolin, etc.), fatty acid esters (palmitic acid) Cetyl, isopropyl palmitate, ethyl linoleate, etc.), higher alcohols (stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol
  • the prophylactic or therapeutic agent of the present invention is used as an external preparation by applying it to a skin site where hypertrophic scar and / or keloid prevention is required, or a hypertrophic scar and / or keloid lesion.
  • the preventive or therapeutic agent of the present invention can effectively prevent or treat hypertrophic scars and / or keloids, for example, skin discoloration (redness, dullness) after a wound / burn, pulling (slipping) It can be used for the purpose of improving, such as lumping, lowering elasticity.
  • the preventive or therapeutic agent of the present invention is a dosage form that can be applied transdermally
  • the formulation form is not particularly limited, and it may be liquid, solid, semi-solid (gel, ointment, paste), etc. Either may be sufficient.
  • the prophylactic or therapeutic agent of the present invention may be in any form of pharmaceutical preparation for external use for skin, cosmetics, skin cleansing agents and the like as long as it is applied to the skin.
  • Specific examples of the preparation form of the preventive or therapeutic agent of the present invention include creams, lotions, gels, emulsions, solutions, patches, aerosols, ointments, packs, and other external skin drugs; ointments, Cosmetics such as creams, emulsions, lotions, lotions, packs and gels; skin cleansing agents such as body shampoos, hair shampoos and rinses.
  • a skin external medicine more preferably a cream, a lotion, a gel, an emulsion, or a pack.
  • the dosage of the preventive or therapeutic agent of this invention according to a formulation form, the grade of the symptom to apply, etc.
  • the dose of the preventive or therapeutic agent of the present invention about 1 to several times a day, in an amount of about 0.1 to 3 mg per 1 cm 2 of skin per application, in terms of the application amount of the component (A)
  • the granulation tissue formation inhibitor of the present invention comprises (A) a heparin-like substance, and (B) allantoin, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof. And used for suppressing the formation of granulation tissue.
  • the types of the components (A) and (B), the preferred components (B), the preferred combinations of the components (B), the components (A) and (B) are the same as in the case of “1. Preventive or therapeutic agent for hypertrophic scar and / or keloid”.
  • the granulation tissue formation inhibitor of the present invention can suppress the formation of granulation tissue, excessive granulation tissue such as hypertrophic scar, keloid, skin swell, discoloration (redness, dullness), tension, lump, reduced elasticity, etc. It can be used for the purpose of preventing or treating skin diseases and skin symptoms caused by natural formation.
  • composition for external use of the present invention comprises (A) a heparin analog, (B-1) at least one selected from the group consisting of allantoin and derivatives thereof, (B-2) glycyrrhizic acid, glycyrrhetinic acid, And at least one selected from the group consisting of derivatives and salts thereof.
  • component (A), component (B-1), and component (B-2), preferred ones thereof, blending amount and ratio thereof, etc. are described in “1. Thickening”. It is the same as in the case of the “prophylaxis or / and keloid preventive or therapeutic agent”.
  • composition for external use of the present invention other components that can be blended in addition to the component (A), the component (B-1), and the component (B-2), the preparation form, the dosage, etc. It is the same as in the case of the “prophylaxis or / and keloid preventive or therapeutic agent”.
  • composition for external use of the present invention has a prophylactic or therapeutic effect on hypertrophic scars and / or keloids and an excellent inhibitory action on granulation tissue formation, such as hypertrophic scars, keloids, skin swelling, redness, tension, lump, etc. Can be suitably used for the purpose of preventing or treating skin diseases and skin symptoms.
  • Test Example 1 Evaluation of granulation tissue formation inhibitory effect
  • a sterilized cotton pellet ("Richmond Cotton Pellet", manufactured by Agusa Japan Co., Ltd.) prepared by adding a small incision on the midline of the back of a 7-week-old (including acclimatization period of 1 week) Slc: Wistar rat. After one was inserted, the incision was sutured.
  • Six hours after the stitching about 1 g of a gel agent shown in Table 1 was applied (initial application) on the skin of the cotton pellet implantation site.
  • About 1 g of the gel shown in Table 1 was applied to the cotton pellet implantation site once a day for a total of 6 days at intervals of 24 hours from the initial application.
  • the granulation formed around the cotton pellet was extracted from the back of the rat together with the cotton pellet. After the extracted granulation was dried, the weight was measured, and this was defined as the granulation dry weight. As a control, the dry weight of granulation was determined in the same manner as described above except that the gel agent was not applied. The value obtained by subtracting the weight of the embedded cotton pellets from the dry weight of the granulation was taken as the granulation weight. In this test, the average granulation weight was calculated using 10 rats per group. Moreover, granulation formation suppression rate (%) was computed from the obtained granulation weight according to the following formula
  • Table 1 shows granulation formation inhibition rates observed by application of each gel agent. From this result, when the heparin-like substance and allantoin are used in combination (Examples 1 and 2), the granulation formation inhibition rate is 1.7 times or more compared to the case of the heparin-like substance alone (Comparative Example 1). It was confirmed that there was an improvement. Furthermore, when heparin-like substances, allantoin, and dipotassium glycyrrhizinate were combined (Example 3), a dramatic improvement in granulation formation inhibition rate was observed.
  • Test Example 2 Evaluation of treatment effect after wound Table 10 shows the therapeutic effects of the creams shown in Table 2 by 10 subjects who have skin swelling (after scuffs or cuts), swell, tension, discoloration (redness, dullness), etc., and who have symptoms of keloids or hypertrophic scars. Evaluated. Specific test methods and test results are as follows.
  • Test method Administration method Specifically, the test subjects were divided into two groups of 5 persons, and in one group, the cream of Example 4 shown in Table 2 was applied to the affected area, and in the other group, the cream of Comparative Example 2 shown in Table 2 was applied. Was applied to the affected area. In both groups, the cream was applied 0.2 g once a day for one month.
  • Test results Table 3 shows the results of visual evaluation of the swell, tension, and discoloration (redness, dullness) of the affected area. From this result, when heparin-like substance, allantoin and dipotassium glycyrrhizinate were used in combination (Example 4), compared to the heparin-like substance alone (Comparative Example 2), the swelled, stiffened, and discolored ( It was confirmed that the therapeutic effect of redness and dullness was high. In particular, the therapeutic effect of the swell of the affected area by the cream of Example 4 was significantly improved as compared with the cream of Comparative Example 2.
  • Table 4 shows the results of skin elasticity measured with a cut meter. Note that the relative value of the skin elasticity of the affected area when the skin elasticity in healthy skin is 1, the lower the elasticity, the lower the elasticity, and the higher the elasticity, the higher the elasticity. As is clear from Table 4, the affected area before application of the cream of Example 4 was less elastic than that of healthy skin, but after application of the cream of Example 4, it was equal to or greater than that of healthy skin. The symptom of the affected area was effectively improved.
  • FIGS. 1 and 2 show the results of 4 subjects in the group to which the cream of Example 4 was applied.
  • FIG. 2 shows the results of 3 subjects in the group to which the cream of Comparative Example 2 was applied. Results are shown.
  • the horizontal axis indicates the hue (Hue), and the closer to the right, the closer to yellow, and the further to the left, the closer to red.
  • the vertical axis indicates lightness (Value), and the higher the value, the brighter the value.
  • Formulation example Creams (Examples 5 to 7) having the compositions shown in Table 5, lotions (Examples 8 to 13) shown in Table 6, gels (Examples 14 to 18) shown in Table 7, and emulsions shown in Table 8 Agents (Examples 19-24) were prepared. As in the case of Test Example 2, all of these preparations are remarkably excellent in the treatment of swelling, stretching, and discoloration (redness, dullness) of the affected area, and effectively prevent keloids and hypertrophic scars. It was confirmed that it could be treated.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)

Abstract

Le problème décrit par la présente invention est de proposer une formulation pharmaceutique à l'aide de laquelle il est possible d'améliorer l'effet prophylactique ou thérapeutique des héparinoïdes sur des cicatrices hypertrophiques et/ou de chéloïdes. La solution de l'invention consiste à utiliser conjointement, (A) les héparinoïdes et (B) l'allantoïne, l'acide glycyrrhizique, l'acide glycyrrhétinique, des dérivés et/ou des sels de ces derniers, grâce à quoi l'effet inhibiteur sur la formation de l'excès de tissu de granulation est plus élevé que lorsque les héparinoïdes sont utilisés seuls, et des cicatrices hypertrophiques et/ou de chéloïdes peuvent être prévenues ou traitées de manière efficace.
PCT/JP2015/070741 2014-07-22 2015-07-21 Composition topique Ceased WO2016013551A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
HK17105154.2A HK1231396B (zh) 2014-07-22 2015-07-21 外用组合物
CN201580040294.3A CN106659713B (zh) 2014-07-22 2015-07-21 外用组合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2014-148570 2014-07-22
JP2014148570 2014-07-22

Publications (1)

Publication Number Publication Date
WO2016013551A1 true WO2016013551A1 (fr) 2016-01-28

Family

ID=55163075

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2015/070741 Ceased WO2016013551A1 (fr) 2014-07-22 2015-07-21 Composition topique

Country Status (3)

Country Link
JP (2) JP5897164B2 (fr)
CN (1) CN106659713B (fr)
WO (1) WO2016013551A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018016596A (ja) * 2016-07-29 2018-02-01 小林製薬株式会社 α−ＳＭＡ産生抑制剤
US20210244707A1 (en) * 2018-06-28 2021-08-12 Kobayashi Pharmaceutical Co., Ltd. External-use composition
JP2022094515A (ja) * 2020-12-15 2022-06-27 小林製薬株式会社 外用組成物

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6851139B2 (ja) * 2016-03-25 2021-03-31 小林製薬株式会社 外用組成物
JP6735587B2 (ja) * 2016-03-25 2020-08-05 小林製薬株式会社 外用組成物
JP6967369B2 (ja) * 2017-05-16 2021-11-17 小林製薬株式会社 乳化組成物
JP7361448B2 (ja) * 2017-05-17 2023-10-16 小林製薬株式会社 トランスグルタミナーゼ発現促進剤
JP2019006697A (ja) * 2017-06-22 2019-01-17 小林製薬株式会社 活性酸素消去剤
JP7197349B2 (ja) * 2018-12-27 2022-12-27 小林製薬株式会社 外用乳化組成物
CN109793757B (zh) * 2019-03-28 2021-06-22 北京刷新活力健康科技有限公司 一种抑制皮肤瘢痕生长的组合物及其制备方法和应用
CN114173757B (zh) * 2019-08-09 2024-10-29 丸善制药株式会社 含有甘草次酸衍生物的组合物

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10330256A (ja) * 1997-05-30 1998-12-15 Kureha Chem Ind Co Ltd グリチルレチン酸化合物含有ｈｓｐ４７合成抑制剤
JP2000143486A (ja) * 1998-11-12 2000-05-23 Lion Corp 皮膚外用剤

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5891651B2 (ja) * 2011-08-19 2016-03-23 株式会社池田模範堂 角層細胞分化正常化用皮膚外用剤
CN103340843B (zh) * 2013-07-11 2014-11-05 中国人民解放军第三军医大学第一附属医院 一种在抑制瘙痒等不适症中应用的高分子复合乳胶疤贴

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10330256A (ja) * 1997-05-30 1998-12-15 Kureha Chem Ind Co Ltd グリチルレチン酸化合物含有ｈｓｐ４７合成抑制剤
JP2000143486A (ja) * 1998-11-12 2000-05-23 Lion Corp 皮膚外用剤

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BEUTH,J. ET AL.: "Safety and Efficacy of Local Administration of ContractubexR to Hypertrophic Scars in Comparison to Corticosteroid Treatment. Results of a Multicenter, Comparative Epidemiological Cohort Study in Germany", IN VIVO, vol. 20, no. 2, 2006, pages 277 - 283 *
MITSUHIRO OSADA ET AL.: "Hikosei Hankon Oyobi Keloid ni Taisuru Besoften Lotion (Heparin Ruiji Busshitsu Lotion-zai) no Rinsho Koka", CLINICAL REPORT, vol. 28, no. 12, November 1994 (1994-11-01), pages 3905 - 3917 *
YOSHIO OSHIMA ET AL.: "Hikosei Hankon Oyobi Keloid ni Taisuru M105101 no Yuyosei no Kento", JOURNAL OF CLINICAL THERAPEUTICS & MEDICINES, vol. 17, no. 7, 19 July 2001 (2001-07-19), pages 1079 - 1087 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018016596A (ja) * 2016-07-29 2018-02-01 小林製薬株式会社 α−ＳＭＡ産生抑制剤
US20210244707A1 (en) * 2018-06-28 2021-08-12 Kobayashi Pharmaceutical Co., Ltd. External-use composition
US12396978B2 (en) * 2018-06-28 2025-08-26 Kobayashi Pharmaceutical Co., Ltd. External-use composition
JP2022094515A (ja) * 2020-12-15 2022-06-27 小林製薬株式会社 外用組成物
JP7709827B2 (ja) 2020-12-15 2025-07-17 小林製薬株式会社 外用組成物

Also Published As

Publication number Publication date
JP2016029025A (ja) 2016-03-03
CN106659713A (zh) 2017-05-10
JP5897164B2 (ja) 2016-03-30
CN106659713B (zh) 2021-09-07
JP2016135787A (ja) 2016-07-28
HK1231396A1 (zh) 2017-12-22

Similar Documents

Publication Publication Date Title
JP5897164B2 (ja) 外用組成物
JP6666068B2 (ja) 外用組成物
JP7153429B2 (ja) 活性酸素消去剤
JP2019006697A (ja) 活性酸素消去剤
JP6725207B2 (ja) 皮膚色素沈着抑制剤
JP6628488B2 (ja) ゲル状外用組成物
JP7313111B2 (ja) 皮脂分泌促進剤及び外用組成物
JP7361448B2 (ja) トランスグルタミナーゼ発現促進剤
JP7446711B2 (ja) 皮膚外用組成物
JP2017171643A (ja) 外用組成物
JP7025129B2 (ja) 筋痙攣治療剤
JP2017186329A (ja) 皮膚色素沈着抑制剤
JP7706218B2 (ja) 皮脂分泌促進剤
JP6735587B2 (ja) 外用組成物
JP7730863B2 (ja) 外用組成物
JP2017088558A (ja) セラミド合成促進剤
JP2021008450A (ja) 角層修復促進剤
JP2017088541A (ja) 異常瘢痕形成抑制剤
JP7610359B2 (ja) 外用組成物
JP7282476B2 (ja) 外用組成物
JP7299682B2 (ja) 皮膚外用組成物
JP7678657B2 (ja) 皮脂分泌促進剤
JP7092498B2 (ja) 尿かぶれ改善剤
HK1231396B (zh) 外用组合物
JP2021195324A (ja) 外用組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15824599

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15824599

Country of ref document: EP

Kind code of ref document: A1