CN106413699B - Externally-applied medicinal composition - Google Patents
Externally-applied medicinal composition Download PDFInfo
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- CN106413699B CN106413699B CN201580028452.3A CN201580028452A CN106413699B CN 106413699 B CN106413699 B CN 106413699B CN 201580028452 A CN201580028452 A CN 201580028452A CN 106413699 B CN106413699 B CN 106413699B
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- 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
- A61K9/08—Solutions
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Abstract
It is an object of the invention to, there is provided in the externally-applied medicinal composition comprising water, containing Diclofenac and/or its salt and tocopherol and/or its derivative and be able to suppress through when or the xanthochromia, the preparation technique with excellent storage stability that generate under the high temperature conditions.By being compounded lactic acid and/or its salt in the externally-applied medicinal composition containing Diclofenac and/or its salt, tocopherol and/or its derivative and water, so as to inhibit through when or the xanthochromia that generates under the high temperature conditions, can have excellent storage stability.
Description
Technical field
The present invention relates to containing Diclofenac and/or its salt, tocopherol and/or its derivative and water and through when or high temperature
Under the conditions of the xanthochromia that generates be suppressed, the externally-applied medicinal composition with excellent storage stability.
Background technique
In modern society, OA equipment popularize caused by prolonged identical posture, excessive pressure, move not
Foot etc. causes the people with shoulder acid, myalgia, arthralgia etc. to increase.In the past, for such shoulder acid, muscle, joint
Pain etc. has carried out the such reply of coating analgesic agent to inhibit the inflammation generated in affected part, improve symptom.
In the past, as analgesic agent, the non-steroid such as Diclofenac, felbinac, dexamethasone, Indomethacin, brufen
Body anti-inflammatory drugs has been practical.It is known that in these non-steroid anti-inflammatory drugs, inhibitory activity of the Diclofenac to cyclooxygenase
It is high and excellent anti-inflammatory analgesic action can be played.Diclofenac is oral or rectal give in the case where, sometimes as side effect
Stomach and intestine, kidney or hepar damnification are generated, also shows serious side effect sometimes especially for stomach and intestine, therefore, recently as
The application of external preparation increases.
In addition, reporting tocopherol acetate in non-patent literature 1 is that representative blood circulation promotes ingredient, for wind
Wet patient reduces side effect when being applied in combination with C14H10Cl2NNaO2, can be true for deformation arthropathy, arthritis, arthralgia etc.
Recognize therapeutic effect.
Existing technical literature
Non-patent literature
Non-patent literature 1:Von H.Bartsch, Fat Sci.Technol.92jahrgang Nr.5 1990,197-
201
Summary of the invention
Problems to be solved by the invention
As shown in non-patent literature 1, it is known that Diclofenac and/or its salt and tocopherol and/or its derivative
Be applied in combination side effect when being applied in combination with C14H10Cl2NNaO2 reduced to rheumatic sufferers, to deformation joint disease, arthritis,
The treatment of arthralgia etc. is effective.Although however, Diclofenac and tocopherol and/or its derivative can preparation turn to capsule
The combination of oral medication such as agent, tablet, but when with being mixed in externally-applied medicinal composition comprising more water, there is external drug combination
Object through when or under the high temperature conditions discoloration be yellow (xanthochromia) and be unable to maintain that transparent appearance character, storage stability reduce
Disadvantage.
Therefore, the object of the present invention is to provide: in the externally-applied medicinal composition comprising water, containing Diclofenac and/
Or its salt and tocopherol and/or its derivative and be able to suppress through when or under the high temperature conditions generate xanthochromia, have it is excellent
Storage stability preparation technique.
The solution to the problem
The present inventor has made intensive studies to solve aforementioned problems, as a result, it has been found that: by containing Diclofenac and/
Or lactic acid and/or its salt are compounded in the externally-applied medicinal composition of its salt, tocopherol and/or its derivative and water, so as to
Inhibit through when or the xanthochromia that generates under the high temperature conditions, can have excellent storage stability.The present invention is based on above-mentioned hair
It now further studies and completes repeatedly.
That is, the present invention provide it is following shown in scheme invention.
1. a kind of externally-applied medicinal compositions, which is characterized in that contain: (A) Diclofenac and/or its pharmaceutically allow
Salt, (B) tocopherol and/or its derivative, (C) lactic acid and/or its salt and (D) water.
2. externally-applied medicinal compositions according to item 1 of item, also contain (E) menthol.
3. externally-applied medicinal compositions according to item 1 or 2 of item, also contain (F) lower alcohol.
4. externally-applied medicinal compositions according to any one of item 1~3 of item, wherein before 0.05~1 weight %
State (C) ingredient.
5. externally-applied medicinal compositions according to any one of item 1~4 of item, wherein before 15~50 weight %
State (D) ingredient.
6. externally-applied medicinal compositions according to any one of item 2~5 of item, wherein contain the aforementioned of 5 weight % or more
(E) ingredient.
7. externally-applied medicinal compositions according to any one of item 1~6 of item, wherein aforementioned (B) ingredient is tocopherol second
Acid esters.
8. externally-applied medicinal compositions according to any one of item 1~7 of item are liquid agent or gelling agent.
A kind of 9. xanthochromia suppressing methods of externally-applied medicinal composition, which is characterized in that containing (A) Diclofenac and/
Or (C) cream is compounded in the externally-applied medicinal composition of its salt, (B) tocopherol and/or its derivative and (D) water for pharmaceutically allowing
Acid and/or its salt.
The effect of invention
Externally-applied medicinal composition according to the present invention, even if Diclofenac and/or its salt, tocopherol and/or its derivative
And water coexists, can also inhibit through when or the xanthochromia that generates under the high temperature conditions, can have excellent storage stability.Into
And in the case that externally-applied medicinal composition of the invention contains 15 weight % or more water more in this way, it is possible to have excellent
Storage stability, therefore, the restriction on formulation design is few, can be used in various pharmaceutical formulations.
In addition, in also containing menthol situation, can also inhibit in Diclofenac in pharmaceutical composition of the invention
And/or under the coexisting of its salt, tocopherol and/or its derivative and water generation precipitation and gonorrhoea, can have transparent height
Excellent appearance character.
In turn, externally-applied medicinal composition of the invention contains Diclofenac and/or its salt and tocopherol and/or its derivative
Object can play excellent anti-inflammatory analgesic action, therefore, can effectively alleviate or cure deformation joint disease, arthritis, joint
Pain etc..
Specific embodiment
1. externally-applied medicinal composition
Externally-applied medicinal composition of the invention is characterized in that, is contained: (A) Diclofenac and/or its pharmaceutically allow
Salt, (B) tocopherol and/or its derivative, (C) lactic acid and/or its salt and (D) water.Hereinafter, to external drug group of the invention
Object is closed to be described in detail.
(A) Diclofenac and/or its salt
Externally-applied medicinal composition of the invention contains Diclofenac and/or its salt (hereinafter, being also denoted as " (A) ingredient " sometimes)
As anti-inflammatory analgesic ingredient.
Diclofenac refers to, the nonsteroidal of also referred to as 2- (2- (2,6- dichlorophenyl amino) phenyl) acetic acid it is known
Compound.
As the salt of Diclofenac, it is not particularly limited using the substance pharmaceutically allowed as limit, for example: sodium
The alkali metal salts such as salt, sylvite；The alkali salts such as calcium salt；With the salt of ammonia；With the alkane such as dimethylamine, diethylamine, trimethylamine, triethylamine
The salt of base primary amine, alkyl secondary amine or alkyl tertiary amine；With monoethanolamine, diethanol amine, diisopropanolamine (DIPA), triethanolamine, three isopropyls
The alkanols such as hydramine primary amine, alkanol secondary amine or salt of alkanol tertiary amine etc..Wherein, alkali metal salt is preferably enumerated, is further preferably enumerated
Sodium salt.The salt of these Diclofenacs pharmaceutically allowed, which can be used alone, can also combine two or more use.
In externally-applied medicinal composition of the invention, as (A) ingredient, a kind of list can be selected from Diclofenac and its salt
It solely uses, two or more use can also be combined.(A) in ingredient, the salt of Diclofenac is preferably enumerated, is further preferably enumerated double
The alkali metal salt of the fragrant acid of chlorine, particularly preferably enumerates C14H10Cl2NNaO2.
For the content of (A) ingredient in externally-applied medicinal composition of the invention, it is not particularly limited, for example,
0.2~2 weight %, preferably 0.5~1.5 weight %, further preferred 0.7~1.3 weight %.
(B) tocopherol and/or its derivative
In order to improve anti-inflammatory analgesic action, externally-applied medicinal composition of the invention contain aforementioned (A) ingredient and tocopherol and/
Or derivatives thereof (hereinafter, being also denoted as " (B) ingredient " sometimes).
Tocopherol is the well known compound as vitamin E.Tocopherol can be any one of d body, l body, dl body,
Preferably dl body.In addition, tocopherol can be any one of α body, β body, γ body, δ body, preferably α body.
It as the derivative of tocopherol, is not particularly limited as long as being limited with the substance pharmaceutically allowed, such as can be with
It enumerates: the ester body with the carboxylic acids such as acetic acid, niacin, succinic acid；With the diester of phosphoric acid etc..It is excellent in the derivative of these tocopherols
It is selected as the ester body with carboxylic acid, further preferably tocopherol acetate.
In addition, the derivative of tocopherol can be any one of d body, l body, dl body, preferably dl body.In turn, tocopherol
Derivative can be α body, β body, γ body, δ body any one, preferably α body.
In externally-applied medicinal composition of the invention, as (B) ingredient, a kind can be selected from tocopherol and its derivative
And be used alone, two or more use can also be combined.(B) in ingredient, the derivative of tocopherol is preferably enumerated, is more preferably enumerated
The ester body of tocopherol and carboxylic acid further preferably enumerates tocopherol acetate, particularly preferably enumerates d- alpha-tocopherol acetate, l-
Alpha-tocopherol acetate, dl- alpha-tocopherol acetate.
For the content of (B) ingredient in externally-applied medicinal composition of the invention, it is not particularly limited, for example,
0.01~2 weight %, preferably 0.05~1.5 weight %, further preferred 0.1~1 weight %.
(C) lactic acid and/or its salt
Externally-applied medicinal composition of the invention contains lactic acid and/or its salt (hereinafter, being also denoted as " (C) ingredient " sometimes).It is logical
Cross can inhibit containing lactic acid and/or its salt through when or the xanthochromia that generates under the high temperature conditions, it is steady to can have excellent preservation
It is qualitative.
As the salt of lactic acid, it is limited with the substance pharmaceutically allowed, is not particularly limited, for example: sodium salt,
The alkali metal salt of sylvite；The alkali salts such as calcium salt, magnesium salts；With the salt of ammonia etc..The salt of these lactic acid can be used alone
Two or more use can be combined.
In externally-applied medicinal composition of the invention, as (C) ingredient, can from lactic acid and its salt a kind of selection and it is independent
It uses, two or more use can also be combined.(C) in ingredient, from the viewpoint of with superior storage stability, preferably
The alkali metal salt of lactic acid, lactic acid is enumerated, lactic acid, sodium lactate is further preferably enumerated, particularly preferably enumerates lactic acid.
For the content of (C) ingredient in externally-applied medicinal composition of the invention, it is not particularly limited, for example,
0.01~1.5 weight %, preferably 0.05~1 weight %, further preferred 0.05~0.6 weight %.
(D) water
The present invention in order to aforementioned (A)~(C) ingredient coexists in water and containing water (hereinafter, be also denoted as sometimes " and (D) at
Point ").
For the content of (D) ingredient in externally-applied medicinal composition of the invention, can suitably be set according to dosage form
It is fixed, for example, 15~50 weight %.In general, making Diclofenac and/or its salt and tocopherol and/or its derivative in water
Content be 15 weight % or more, particularly up to 20 weight % or more under conditions of when coexisting, through when or under the high temperature conditions produce
Raw xanthochromia is obvious, but for externally-applied medicinal composition of the invention, so containing in the case where more water, can also inhibit to pass through
When or the xanthochromia that generates under the high temperature conditions.If in view of such effect of the invention, as external drug of the invention
The content of (D) ingredient in composition, preferably enumerates 15~45 weight %, further preferably enumerates 20~45 weight %, especially
It is preferred that 20~24 weight % are enumerated, it is optimal to elect 20.3~23.3 weight %.
(E) menthol
Externally-applied medicinal composition of the invention can according to need containing menthol (hereinafter, be also sometimes referred to as " and (E) at
Point ").By containing menthol, being total in Diclofenac and/or its salt and tocopherol and/or its derivative and water can be inhibited
The gonorrhoea for leaving generation can have the high excellent appearance character of the transparency.It in turn, can be to institute by containing menthol
The skin of application assigns refrigerant sense, so that use feeling is good.
Menthol is any one of d body, l body, dl body, preferably enumerates l body.
In addition, the essential oil comprising menthol, which can be used, in externally-applied medicinal composition of the invention is used as (E) ingredient.Comprising thin
The essential oil of lotus can suitably be selected from well known substance and be used, for example: peppermint oil, peppermint
(peppermint) oil, spearmint (spearmint) oil etc..
(E) in ingredient, from further effectively inhibiting in Diclofenac and/or its salt, tocopherol and/or its derivative
Under coexisting with water from the perspective of the gonorrhoea of generation and precipitate, l-menthol and the essential oil comprising it are preferably enumerated.
For the content of (E) ingredient in externally-applied medicinal composition of the invention, it is not particularly limited, for example,
1 weight % or more, preferably 1~15 weight %, further preferred 3~10 weight %, particularly preferred 5~10 weight %, most preferably 5
~8 weight %.
(F) lower alcohol
Can according to need in externally-applied medicinal composition of the invention containing lower alcohol (hereinafter, be also sometimes referred to as (F) at
Point).By containing lower alcohol, coexisting in Diclofenac and/or its salt, tocopherol and/or its derivative and water can be inhibited
The gonorrhoea of lower generation and the generation of precipitate.
As lower alcohol, be not particularly limited, for example: ethyl alcohol, propyl alcohol, isopropanol, n-butanol, sec-butyl alcohol,
The unitary lower alcohol of the carbon numbers such as the tert-butyl alcohol 1~4.Wherein, from effectively further inhibiting in Diclofenac and/or its salt, fertility
Under the coexisting of phenol and/or its derivative and water from the perspective of the gonorrhoea of generation and precipitate, ethyl alcohol, propyl alcohol, different is preferably enumerated
Propyl alcohol further preferably enumerates ethyl alcohol.These lower alcohols, which can be used alone, can also combine two or more use.
For the content of (F) ingredient in externally-applied medicinal composition of the invention, it is not particularly limited, for example,
50~80 weight %, preferably 55~75 weight %, further preferred 55~70 weight %.
Other compositions
As long as effect of the invention is not interfered in externally-applied medicinal composition of the invention, according to need other than aforesaid ingredients
Pharmaceutical component can also be contained.For the pharmaceutical component that can be compounded in externally-applied medicinal composition of the invention, without spy
It does not limit, for example: the anti-inflammatory agents such as enoxolone, dipotassium glycyrrhizinate, ammonium glycyrrhetate, glycyrrhizic acid stearyl ester；Diphenyl
The antihistaminics such as imidazoles, diphenhydramine and its salt pharmaceutically allowed, chlorphenamine maleate；Lidocaine is pharmaceutically permitted with it
The local anesthetics such as salt perhaps, cincaine and its salt pharmaceutically allowed, benzocaine；Nicotinic acid benzyl ester, n-nonanoic acid are fragrant
The blood circulation accelerants such as oxamides, pepper extract；Arnica tincture, phellodendron extract, mountain Cape jasmine seed extract, horse-chestnut are extracted
Crude drugs such as object, Tangut Anisodus Radix extract, belladonna extract, angelica extract, strike extract, Chinese pepper extract etc..
In addition, in externally-applied medicinal composition of the invention, also may include in addition to preceding to be made desired dosage form
State the bases such as aqueous base, the oiliness base other than (D) and (F) ingredient.
As the aqueous base other than aforementioned (D) and (F) ingredient, for example: glycerol, propylene glycol, dipropyl
Polyalcohols such as glycol, butanediol etc..
It as oiliness base, can enumerate: non-polar oil, polar oil etc..As non-polar oil, specifically, can lift
Out: the hydro carbons such as alkane, isomerization alkanes；Saualane, wax etc..In addition, as polar oil, specifically, can enumerate: fat
Race monocarboxylate, glyceryl ester, aliphatic dicarboxylic acid diester, aliphatic dicarboxylic acid alkylidene diol ester, higher fatty acids etc..
In turn, externally-applied medicinal composition of the invention also may include external drug as needed other than aforesaid ingredients
Other usually used additives in composition.As such additive, for example: pH adjusting agent, surface-active
Agent, emulsifier, solubilizer, preservative, preservative agent, antioxidant, stabilizer, chelating agent, thickener, fragrance, colorant etc..It is right
The thickener that can be compounded in externally-applied medicinal composition of the invention, is not particularly limited, for example: hydroxypropyl is fine
Tie up element, hypromellose, hydroxyethyl cellulose, carboxy vinyl polymer, hyaluronic acid, xanthan gum etc..
pH
The pH of externally-applied medicinal composition as invention, can percutaneously using in the range of suitably set, such as
3.0~9.0, preferably 4.0~9.0, further preferred 4.5~9.0 can be enumerated.
Dosage form
Do not have for the dosage form of externally-applied medicinal composition of the invention using the form that can percutaneously apply as limit
Especially limitation, for example: liquid agent (including distillate medicinal water, spray, aerosol and emulsion agent), foaming agent, ointment, frost
Agent, gelling agent, patch etc..Wherein, liquid agent or gelling agent are preferably enumerated.To the preparation of these dosage forms can as follows into
Row: according to the well known method recorded in the 16th revision Japanese Pharmacopoeia preparation general provisions etc., the addition for meeting dosage form is used
Agent carries out formulation.
Usage mode
The externally-applied medicinal composition of invention is by the way that analgesic is needed, locally (skin) topical administration is used.Of the invention is outer
The amount of giving of pharmaceutical composition according to the position given, the symptom that should be treated degree etc. and suitably set, preferably to every
1cm2Every 1 amount of giving of the part of administration, Diclofenac and/or its salt pharmaceutically allowed is 10~500mg left
Right amount.
Externally-applied medicinal composition of the invention can be used as externally applied anti-inflammation analgestic, can be used for therapeutic purposes with shoulder
Pain, arthralgia, pain in the loins, courbature, tenosynovitis (hand/wrist pain), pain (tennis elbow etc.), the bruise of elbow of the shoulder of acid
Bitterly, pain, fracture pain, neuralgia, morphotropism joint disease, arthritis etc. are sprained.
2. xanthochromia suppressing method
In turn, the present invention provides: inhibit containing (A) Diclofenac and/or its salt pharmaceutically allowed, (B) tocopherol and/
Or derivatives thereof and (D) water externally-applied medicinal composition through when or the method for xanthochromia that generates under the high temperature conditions.Specifically
For, xanthochromia suppressing method of the invention is characterized in that, containing (A) Diclofenac and/or its salt pharmaceutically allowed,
(B) (C) lactic acid and/or its salt are compounded in the externally-applied medicinal composition of tocopherol and/or its derivative and (D) water.The present invention
Xanthochromia suppressing method in, for the type of the ingredient used, compounding amount, the pH of externally-applied medicinal composition, dosage form etc., such as
Described in the column of aforementioned " 1. externally-applied medicinal composition ".
Embodiment
Hereinafter, showing embodiment further illustrates the present invention, but the present invention is not limited to these.
Test example 1
Prepare the externally-applied medicinal composition of composition shown in table 1 and 2.Specifically, adding rule in the ethyl alcohol of specified amount
Quantitative C14H10Cl2NNaO2 and l-menthol (only the case where Examples 1 and 2), make it dissolve, and then add the fertility of specified amount
Phenol acetic acid esters (dl- alpha-tocopherol acetate) and lactic acid or sodium lactate simultaneously stir.Then, water and the hydroxypropyl for adding specified amount are fine
It ties up plain (only the case where embodiment 2) and stirs, (be liquid other than embodiment 2, implement to obtain externally-applied medicinal composition
Example 2 is gel).
Each externally-applied medicinal composition of gained is saved 1 week under dark conditions at 60 DEG C.Front and back is saved with visual valuation
Appearance character.It should be noted that the evaluation of appearance character is specifically carried out according to determinating reference below.
The determinating reference > of < appearance character
◎: for colorless and transparent and there is no gonorrhoeas.
Zero: gonorrhoea occurs, but does not confirm the tone of yellow, is colourless.
△: having occurred gonorrhoea, and then confirms the tone for being equivalent to the yellow of PANTONE 712C.
×: gonorrhoea has occurred, and then confirms the tone for being equivalent to the yellow of PANTONE 713C.
××: having occurred gonorrhoea, and then confirms the tone for being equivalent to the yellow of PANTONE 714C or 715C.
It should be noted that PANTONE 712C, 713C, 714C, 715C refer to, the color sample of Pantone company distribution
In this Formulaguide solid coated color card number, show the tone of yellow, according to 712C < 713C <
The concentration of the sequence of 714C < 715C, yellow increases.
Acquired results are shown in table 1 and 2.In the presence of water, it when C14H10Cl2NNaO2 and tocopherol acetate coexists, saves
After confirm xanthochromia (comparative example 1~3).In particular, further acknowledging the generation of precipitate in comparative example 1.In addition, existing in water
Under, C14H10Cl2NNaO2, tocopherol acetate and acetic acid coexists, xanthochromia (comparative example 2) is also confirmed after preservation.On the other hand,
In the presence of water, when C14H10Cl2NNaO2, tocopherol acetate and lactic acid or sodium lactate coexists, tone does not also become after preservation
Change, xanthochromia (Examples 1 to 10) can also be inhibited.In addition, in the presence of water, making C14H10Cl2NNaO2, tocopherol acetate also
When lactic acid and menthol coexist, gonorrhoea can be inhibited, colorless and transparent state (Examples 1 and 2) is also kept after preservation.
[table 1]
In table, respectively the unit containing ingredient is " weight % ".
[table 2]
In table, respectively the unit containing ingredient is " weight % ".
Preparation example
Preparing the shown externally-applied medicinal composition formed of table 3, (preparation example 1,3 and 5 is liquid；Preparation example 2,4 and 6 is gel
Shape).Gained externally-applied medicinal composition is provided with colorless and transparent excellent appearance character, and 1 week is saved at 60 DEG C also without true
Recognize xanthochromia, gonorrhoea.
[table 3]
In table, respectively the unit containing ingredient is " weight % ".
Claims (8)
1. a kind of externally-applied medicinal composition, which is characterized in that contain: the Diclofenac of (A) 0.2 ~ 2 weight % and/or its pharmaceutically
The lactic acid and/or its salt of the salt of permission, the tocopherol of (B) 0.01 ~ 2 weight % and/or its derivative, (C) 0.01 ~ 1.5 weight %
And the water of (D) 15 ~ 50 weight %, and the nicotinic acid benzyl ester of 0.01 weight % is not contained, the derivative of the tocopherol is selected from fertility
It is one kind or two or more in the diester of the ester body of phenol and carboxylic acid, tocopherol and phosphoric acid.
2. externally-applied medicinal composition according to claim 1 also contains (E) menthol.
3. externally-applied medicinal composition according to claim 1 or 2 also contains (F) lower alcohol.
4. externally-applied medicinal composition according to claim 1 or 2, wherein contain (C) ingredient of 0.05 ~ 1 weight %.
5. externally-applied medicinal composition according to claim 2, wherein contain (E) ingredient described in 5 weight % or more.
6. externally-applied medicinal composition according to claim 1 or 2, wherein (B) ingredient is tocopherol acetate.
7. externally-applied medicinal composition according to claim 1 or 2 is liquid agent or gelling agent.
8. a kind of xanthochromia suppressing method of externally-applied medicinal composition, which is characterized in that fragrant in double chlorine containing (A) 0.2 ~ 2 weight %
Acid and/or its salt pharmaceutically allowed, the tocopherol of (B) 0.01 ~ 2 weight % and/or its derivative and (D) 15 ~ 50 weight %
Water, and without containing 0.01 weight % nicotinic acid benzyl ester externally-applied medicinal composition in be compounded (C) 0.01 ~ 1.5 weight % lactic acid
And/or its salt, the derivative of the tocopherol in the diester of the ester body of tocopherol and carboxylic acid, tocopherol and phosphoric acid 1
Kind or two or more.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014-070677 | 2014-03-30 | ||
| JP2014070677A JP6599083B2 (en) | 2014-03-30 | 2014-03-30 | Pharmaceutical composition for external use |
| PCT/JP2015/059321 WO2015151989A1 (en) | 2014-03-30 | 2015-03-26 | Pharmaceutical composition for external use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106413699A CN106413699A (en) | 2017-02-15 |
| CN106413699B true CN106413699B (en) | 2019-12-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580028452.3A Active CN106413699B (en) | 2014-03-30 | 2015-03-26 | Externally-applied medicinal composition |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JP6599083B2 (en) |
| CN (1) | CN106413699B (en) |
| MY (1) | MY180369A (en) |
| SG (1) | SG11201608122PA (en) |
| TW (1) | TWI673050B (en) |
| WO (1) | WO2015151989A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102292068A (en) * | 2009-01-30 | 2011-12-21 | 克迪斯药品有限公司 | Transdermal delivery of diclofenac, carbamazepine and benzydamine |
| CN105246471A (en) * | 2013-03-29 | 2016-01-13 | 小林制药株式会社 | Pharmaceutical composition for external application |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2058975C (en) * | 1990-10-30 | 2000-06-06 | Shuichi Kasai | Antiinflammatory gel preparation |
| JP3100408B2 (en) * | 1991-03-26 | 2000-10-16 | 株式会社資生堂 | Skin external preparation containing diclofenac sodium |
| JPH11255644A (en) * | 1998-03-09 | 1999-09-21 | Lintec Corp | Percutaneous absorption type antipyretic antiphlogistic analgesic |
| US7138394B2 (en) * | 2002-09-27 | 2006-11-21 | Alpharx Inc. | Vehicle for topical delivery of anti-inflammatory compounds |
| JP4820065B2 (en) * | 2004-05-24 | 2011-11-24 | 同仁医薬化工株式会社 | Anti-inflammatory analgesic topical aqueous solution |
| AR051397A1 (en) * | 2004-10-21 | 2007-01-10 | Novartis Ag | PHARMACEUTICAL COMPOSITION |
| CH699814B1 (en) * | 2007-05-14 | 2010-05-14 | Mepha Ag | Diclofenac for topical application as a spray. |
| CN101790370B (en) * | 2007-06-08 | 2013-06-12 | 特罗伊卡药品有限公司 | A novel non-aqueous topical solution of diclofenac and process for preparing the same |
| BR112014005358A8 (en) * | 2011-09-09 | 2017-10-03 | Propella Therapeutics Inc | COMPOSITIONS COMPRISING TRPV1 SELECTIVE AGONIST AND THEIR USES |
-
2014
- 2014-03-30 JP JP2014070677A patent/JP6599083B2/en active Active
-
2015
- 2015-03-26 SG SG11201608122PA patent/SG11201608122PA/en unknown
- 2015-03-26 TW TW104109750A patent/TWI673050B/en active
- 2015-03-26 MY MYPI2016703599A patent/MY180369A/en unknown
- 2015-03-26 WO PCT/JP2015/059321 patent/WO2015151989A1/en active Application Filing
- 2015-03-26 CN CN201580028452.3A patent/CN106413699B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102292068A (en) * | 2009-01-30 | 2011-12-21 | 克迪斯药品有限公司 | Transdermal delivery of diclofenac, carbamazepine and benzydamine |
| CN105246471A (en) * | 2013-03-29 | 2016-01-13 | 小林制药株式会社 | Pharmaceutical composition for external application |
Non-Patent Citations (1)
| Title |
|---|
| 促进透皮吸收的中药(一);张仲源;《中医外治杂志》;20010630;第10卷(第3期);第48-49页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106413699A (en) | 2017-02-15 |
| TWI673050B (en) | 2019-10-01 |
| JP2015189759A (en) | 2015-11-02 |
| SG11201608122PA (en) | 2016-11-29 |
| WO2015151989A1 (en) | 2015-10-08 |
| TW201622711A (en) | 2016-07-01 |
| MY180369A (en) | 2020-11-28 |
| JP6599083B2 (en) | 2019-10-30 |
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