CN1938011A - Pharmaceutical product containing tranilast - Google Patents
Pharmaceutical product containing tranilast Download PDFInfo
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- CN1938011A CN1938011A CN 200580010121 CN200580010121A CN1938011A CN 1938011 A CN1938011 A CN 1938011A CN 200580010121 CN200580010121 CN 200580010121 CN 200580010121 A CN200580010121 A CN 200580010121A CN 1938011 A CN1938011 A CN 1938011A
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Abstract
A pharmaceutical product comprising a package not only permitting viewing of its interior but also capable of inhibiting the decomposition of tranilast by light and, accommodated therein, a pharmaceutical preparation containing tranilast. The pharmaceutical product is produced by accommodating a pharmaceutical preparation containing tranilast and/or a salt thereof in a package permitting viewing of its interior, the package provided with light shielding means that blocks light of 350 to 450 nm wavelength region.
Description
Technical field
The present invention relates to contain the drug products of tranilast.More particularly, the pharmaceutical preparation that the present invention relates to wherein to contain tranilast is accommodated in the drug products in the packing container, sees through this container and can be visually observed the light degradation that content and this container can prevent tranilast.The present invention relates to be used to suppress the photodegradative method of tranilast.
Background of invention
(N-(3,4-dimethoxy cinnamoyl) the oral allergic disease that is used for the treatment of of ortho-aminobenzoic acid is such as bronchial asthma, allergic rhinitis etc. for tranilast.Tranilast also is used as eye drop with the treatment allergic disease at present.Usually, because tranilast is in that to be exposed to the light time extremely unstable, therefore during preparation and/or be exposed to the stability that the light time it is highly important that the pharmaceutical preparation of guaranteeing to contain tranilast after opening.Contain the stability of formulation of the pharmaceutically active substance of photo-labile is guaranteed usually in the following way: be poured over this preparation in brown or the aluminium vessel and/or the container that will hold this preparation is kept in the bag to prevent that light from penetrating.
Preferably will be contained in through it and can be visually observed in the transparent vessel of content, to make it to check existing of foreign substance such as the pharmaceutical preparation of eye drop, collyrium, injection etc.What also wish for user in addition, is the container transparent of holding pharmaceutical preparation to a certain degree so that the content that can detect by an unaided eye is checked surplus.
Up to the present, use brown glass container to hold the pharmaceutical preparation that contains tranilast always.But the problem that existing brown container faces is to guarantee the stability of tranilast to light fully.In addition, a shortcoming that can intercept the aluminum of light or opaque containers fully is that the state or the amount of the pharmaceutical preparation that wherein stores can not be from the container visual examination, and this has caused the inconvenience aspect production process management and quality control.In addition, for the user very inconvenience be to carry/preserve to be placed on not make to contain tranilast pharmaceutical preparation container in the pocket that light passes through, the stability of even now tranilast can be guaranteed.
For example from the viewpoint of the prescription of pharmaceutical preparation, patent document 1 has proposed a kind of method of improving the medicine light stability; But wherein not open packing container by the improvement storage of pharmaceutical keeps any method of medicine to the stability of light.
In view of prior art, the pharmaceutical preparation that needs exploitation will contain tranilast is kept at the method in the container, sees through the light degradation that this container can be visually observed content and can prevent tranilast.
Patent document 1: the open No.2003-26575 of Japanese unexamined patent.
Summary of the invention
The problem to be solved in the present invention
The invention is intended to provide a kind of pharmaceutical preparation that will contain tranilast to be contained in drug products in the container, see through the light degradation that this container can be visually observed content and can suppress tranilast.The present invention also is intended to provide a kind of photodegradative method that is used to suppress tranilast.
The mode that addresses this problem
In view of the above problems, the inventor has carried out extensive studies, and find that working as the degraded that is exposed to the light time tranilast is to be caused by the light of wave-length coverage at 365nm-430nm, has therefore realized the Photostabilised of tranilast by the light that intercepts in this scope.Find to have finished the present invention based on these through further studying.
More particularly, the invention provides following drug products:
1. 1 kinds of drug products of project are included in the pharmaceutical preparation that contains tranilast and/or its salt in the packing container, and it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
Project 3. is according to the drug products of project 2, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-430nm.
Project 4. is according to the drug products of project 1, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-450nm.
The drug products that project 5. is any one according to project 1-4, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm, at wave-length coverage 350nm-430nm is 20% or lower, and is 20% or lower at wave-length coverage 350nm-430nm.
The drug products that project 6. is any one according to project 1-5, the part of wherein said packing container is 30% or higher at the average transmittance of wave-length coverage 455nm-780nm.
The drug products that project 7. is any one according to project 1-6, wherein said pharmaceutical preparation also comprise at least a following component (B) that is selected from: berberine, vitamin B2, Hesperidin, hydroxyquinoline, vitamin B12, their derivant and their salt.
The drug products that project 8. is any one according to project 1-7, wherein said pharmaceutical preparation is aqueous formulation.
Project 9. is according to the drug products of project 8, and wherein the amount toatl proportion of tranilast and/or its salt is 0.01-20 weight %, based on the total amount of pharmaceutical preparation.
The drug products that project 10. is any one according to project 1-9, wherein said pharmaceutical preparation are eye drop, collyrium, injection, external skin medicament, nasal drop or contact lenses nursing agent.
11. 1 kinds of drug products of project comprise packing container (i) and pharmaceutical preparation (ii), wherein
Described packing container (i) is that a kind of to see through its content be visible and intercept the material of wave-length coverage at the light of 365nm-430nm, and
Described pharmaceutical preparation (ii) comprises tranilast and/or its salt, and is accommodated in the described packing container (i).
The present invention also provides and has been used to prevent photodegradative following method:
Project is used to suppress tranilast or the photodegradative method of its salt for 12. 1 kinds, comprise that will contain at least a component pharmaceutical formulation that is selected from tranilast and salt thereof places packing container, it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
Project 13. is according to the method for project 12, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm.
Project 14. is according to the method for project 13, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-430nm.
Project 15. is according to the method for project 13, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-450nm.
The method that project 16. is any one according to project 12-15, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm, at wave-length coverage 350nm-430nm is 20% or lower, and is 20% or lower at wave-length coverage 350nm-430nm.
The method that project 17. is any one according to project 12-16, the part of wherein said packing container is 30% or higher at the average transmittance of wave-length coverage 455nm-780nm.
The method that project 18. is any one according to project 12-17, wherein said pharmaceutical preparation also comprise at least a following component (B) that is selected from: berberine, vitamin B2, Hesperidin, hydroxyquinoline, vitamin B12, their derivant and their salt.
The method that project 19. is any one according to project 12-18, wherein said pharmaceutical preparation is aqueous formulation.
The method that project 21. is any one according to project 12-20, wherein said pharmaceutical preparation are eye drop, collyrium, injection, external skin medicament, nasal drop or contact lenses nursing agent.
Project is used to make the Photostabilised method of drug products that contains tranilast and/or its salt for 22. 1 kinds, comprise that the pharmaceutical preparation that will contain tranilast and/or its salt (ii) is placed in the packing container (i), it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
In addition, according to the present invention, use to intercept wave-length coverage and suppressed at least a component that is selected from tranilast and salt thereof at the transparent wrapper container of the light of 365nm-430nm and be exposed to the degraded of light time.Therefore, the invention provides following purposes.
Project 23. packing containers are used to suppress at least a component that is selected from tranilast and salt thereof in the purposes that is exposed to the light time degraded, and it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
Project 24. is according to the purposes of the packing container of project 23, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 360nm-430nm.
Project 25. is according to the purposes of the packing container of project 24, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-430nm.
Project 26. is according to the purposes of the packing container of project 24, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-450nm.
Project 27. is according to the purposes of any one packing container of project 23-26, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm, at wave-length coverage 350nm-430nm is 20% or lower, and is 20% or lower at wave-length coverage 350nm-430nm.
Project 28. is according to the purposes of any one packing container of project 23-27, and the part of wherein said packing container is 30% or higher at the average transmittance of wave-length coverage 455nm-780nm.
In addition, be visible and intercept the packing container of wave-length coverage by using at the light of 365nm-430nm through its content, the present invention can prevent to contain at least a component pharmaceutical formulation that is selected from tranilast and salt thereof and be exposed to the degraded of light time, and guarantees light stability.Therefore, the invention provides following purposes.
Project 31. is according to the purposes of the packing container of project 30, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-430nm.
Project 32. is according to the purposes of the packing container of project 30, and wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-450nm.
Project 33. is according to the purposes of any one packing container of project 29-32, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm, at wave-length coverage 350nm-430nm is 20% or lower, and is 20% or lower at wave-length coverage 350nm-430nm.
Project 34. is according to the purposes of any one packing container of project 29-33, and the part of wherein said packing container is 30% or higher at the average transmittance of wave-length coverage 455nm-780nm.
The accompanying drawing summary
Fig. 1 is illustrated in the light transmittance of the red membrane that uses in the test implementation example 1.
Fig. 2 is illustrated in the light transmittance of the yellow film that uses in the test implementation example 1.
Fig. 3 is illustrated in the light transmittance of the green film of using in the test implementation example 1.
Fig. 4 is illustrated in the test implementation example 1 light transmittance of the Huang-green container that uses, made by polyethylene terephthalate.
Fig. 5 is illustrated in the light transmittance of the reddish violet film that uses in the test implementation example 1.
Fig. 6 is illustrated in the light transmittance of the transparent glass container that uses in the test implementation example 1.
Fig. 7 is illustrated in the test implementation example 1 light transmittance of the transparent vessel that uses, made by polypropylene.
Fig. 8 is illustrated in the test implementation example 1 light transmittance of the brown container that uses, made by polypropylene.
Fig. 9 is illustrated in the light transmittance of the blue film of using in the test implementation example 1.
Figure 10 is illustrated in the light transmittance of the double-deck blue film of using in the test implementation example 1.
Figure 11 is illustrated in the light transmittance of three layers of blue film using in the test implementation example 1.
Implement best mode of the present invention
In this manual, aqueous pharmaceutical preparations is meant that the aqueous ratio of bag is 5 weight % or more, preferred 20 weight % or more, also further preferred 50 weight % or more pharmaceutical preparation, based on the total amount of pharmaceutical preparation.
I. drug products
The present invention relates to a kind of drug products, the pharmaceutical preparation that wherein contains tranilast and/or its salt is accommodated in the packing container, and it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
More specifically, the present invention relates to a kind of drug products, comprise packing container (i) and pharmaceutical preparation (ii), wherein:
Described packing container (i) is that a kind of to see through its content be visible and intercept the material of wave-length coverage at the light of 365nm-430nm, and
Described pharmaceutical preparation (ii) comprises tranilast and/or its salt, and is accommodated in the described packing container (i).
(i) packing container
The packing container that is used for drug products of the present invention is that a kind of to see through its content be visible and intercept the packing container of wave-length coverage at the light of 365nm-430nm.
In the present invention, " packing container " not only is meant the packing container (hereinafter being referred to as " primary package container ") that directly holds pharmaceutical preparation, and primary package container is meant and directly holds pharmaceutical preparation in packing container wherein under being meant the one or more packing containers (hereinafter being referred to as " secondary package container ") that are used for holding primary package container.
When drug products of the present invention had the secondary package container, the primary package container of necessary is drug products at least or secondary package container intercepted the light in the above-mentioned wave-length coverage.From not only distributing and between the storage life but also all should prevent to be contained in the tranilast the packing container or the viewpoint of its salt degraded during use, preferably be that primary package container intercepts the light in the above-mentioned wave-length coverage at least.
Can use arbitrary form packing container and without limits, as long as the said medicine preparation can be accommodated in wherein, and can be according to the form and/or the desired use of the pharmaceutical preparation that will hold, or purpose purposes, promptly be primary package container or secondary package container etc., suitably select the form of packing container.The object lesson that is used as the packing container form of primary package container comprises sachet type (pouch type) packing container, tubular container, flask, PTP packing container, eye lotion dropper, nose-dropper etc.In addition, the example as the packing container form that is used as the secondary package container has form pillow packs bag etc.
In the present invention, " seeing through its content is visible packing container " is meant the packing container with content visuality, and promptly packing container has transparency to a certain degree so that the content that is contained in the packing container can observe with the naked eye.The object lesson of " see through its content is visible packing container " be included in the visible-range of 455nm-780nm average transmittance be 30% higher, preferred 40% or higher, more preferably 50% or higher, preferred especially 70% or higher packing container (hereinafter being referred to as " average transmittance in the 455nm-780nm wave-length coverage ").Favourable part with packing container of average transmittance in the above-mentioned 455nm-780nm wave-length coverage is that the visuality of content is guaranteed in this packing container.In the present invention, light transmittance is measured according to the method for stipulating among the JIS K7105.Average transmittance can and calculate meansigma methods with the light transmittance of measuring and determine by every 5nm measurement light transmittance in the 455nm-780nm wave-length coverage in the 455nm-780nm wave-length coverage.
In the present invention, when part provided the content visuality (transparency) of packing container, the pharmaceutical preparation in the packing container just can be seen from the outside.Therefore, needn't on the whole surface of packing container, guarantee content visuality (transparency).For example, hold at packing container under the situation of pharmaceutical preparation such as eye drop and injection, from being determined the viewpoint of the existence of insoluble foreign substance by the outside, its sidewall can have at least 80% or higher content visuality (transparency), preferred 90% or higher.Container side wall is meant lateral parts as used herein, promptly uses the part of cap covers and the part the bottom in the whole surface of container.In addition, even when when the stage of for example distributing will show that the label of composition and trade name is applied on the packing container surface, the content visuality (transparency) of packing container of the present invention can not reduce yet.But preferably apply label in following this mode: fully guarantee provides the part of content visuality (transparency) so that user can be checked the amount that is included in the pharmaceutical preparation in the packing container.
In the present invention, " intercepting the light of wave-length coverage at 365nm-430nm " and be meant average transmittance at wave-length coverage 365nm-430nm is 20% or lower (hereinafter being referred to as " average transmittance in the 365nm-430nm wave-length coverage ").The same with the situation of average transmittance in the 455nm-780nm wave-length coverage, average transmittance can be measured according to the method for stipulating among the JIS K7105 in the 365nm-430nm wave-length coverage.More particularly, determine by every 5nm measurement light transmittance in the 365nm-430nm wave-length coverage and with the light transmittance calculating meansigma methods of measuring.
From more effectively suppressing the photodegradative viewpoint of tranilast and salt thereof, preferably use in the 365nm-430nm wave-length coverage average transmittance preferred 15% or lower, more preferably 10% or lower, preferred especially 3% or lower container.
In order to give more excellent light stability for the pharmaceutical preparation comprise tranilast and/or its salt, preferred be to use average transmittance (hereinafter being referred to as " average transmittance in the 350nm-450nm wave-length coverage ") at wave-length coverage 350nm-450nm be 20% lower, preferred 15% or lower, more preferably 10% or lower, still more preferably 5% or lower, preferred especially 3% or lower container.Average transmittance is determined in the mode the same with the situation of average transmittance in the 365nm-430nm wave-length coverage in the 350nm-450nm wave-length coverage.
Can mention that a preferred aspect as packing container of the present invention is, for example packing container the average transmittance (hereinafter being referred to as " average transmittance in the 350nm-450nm wave-length coverage ") of wave-length coverage 350nm-450nm be 20% lower, preferred 15% or lower, more preferably 10% or lower, still more preferably 5% or lower, preferred especially 3% or lower.Average transmittance is determined in the mode the same with the situation of average transmittance in the 365nm-430nm wave-length coverage in the 350nm-450nm wave-length coverage.
In addition, can mention that another the preferred aspect as packing container of the present invention is, for example the average transmittance of packing container in wave-length coverage is each scope of 365nm-430nm, 350nm-450nm and 350nm-450nm be 20% lower, preferred 15% or lower, more preferably 10% or lower, still more preferably 5% or lower.
Therefore, the packing container that employing can intercept the light in the above-mentioned wave-length coverage prevents that light from penetrating wherein, and the tranilast in the packing container or the stability of its salt can be guaranteed.
For the method that intercepts the light in the 365nm-430nm wave-length coverage with packing container without limits, as long as guarantee the average transmittance that above-mentioned 455nm-780nm wave-length coverage is interior.For example, can intercept light by in packing container, adding the material that can intercept the light in the 365nm-430nm wave-length coverage.
For the material that can intercept the light in the 365nm-430nm wave-length coverage without limits.This examples of substances comprises that the Chinese spreads pigment, benzimidazoline pigment, pyrazolone pigments and similar monoazo pigment; Diaryl thing pigment, pyrazorone pigment and similar disazo pigment; The flavochrome and the AZOpigments that similarly contracts; Putalocyanine pigment, perinone pigment, isoindolinone pigment, anthraquinone pigment and similar condensation polycyclic pigment etc.These materials that can intercept the light in the 365nm-430nm wave-length coverage can be used singly or in combination.
Particularly preferred example of following compounds (1)-(28) as the material that can intercept the light in the 365nm-430nm wave-length coverage proposed.Unless specify in addition in this manual, otherwise chemical compound (1)-(26) are represented according to chemical abstracts service (CAS).
(1) azo 4-[[3-[(3,5-dimethylphenyl)]-2, the 4-dihydroxy phenyl] azo]-benzenesulfonic acid,
(2) 2-(1,3-dioxy indane-2-yl)-quinoline disulfonic acid, (IUPAC:2-(1,3-dioxy indane-2-yl) quinoline disulfonic acid),
(3) 2-(1,3-dioxy indane-2-yl)-quinoline, (IUPAC:2-(1,3-dioxy indane-2-yl)-quinoline, common name (color index title): solvent yellow 33),
(4) 2,2 '-[(3,3 '-dichloro [1,1 '-xenyl]-4,4 '-two bases) bisazo] two [3-oxygen-N-phenyl] butyramide, (common name (color index title): pigment Yellow 12),
(5) azo 2-[(4-methyl-2-nitrobenzophenone)]-3-oxygen-N-phenyl-butyramide, (common name (color index title): pigment yellow 1),
(6) 5-chloro-2-[4,5-dihydro-3-methyl-4-[[4-[[(4-aminomethyl phenyl) sulfonyl] oxygen] phenyl] azo]-5-oxygen-1H-pyrazol-1-yl]-benzenesulfonic acid,
(7) 8-hydroxyl-5,7-dinitro-2-LOMAR PWA EINECS 246-676-2,
(8) 1-(phenylazo)-2-naphthylamines, (common name (color index title): solvent yellow 5),
(9) azo 1-[(2-aminomethyl phenyl)]-the 2-naphthylamines, (common name (color index title): solvent yellow 6),
(10) 3-[[4-(phenyl amino) phenyl] azo]-benzenesulfonic acid, (common name (color index title): Indian yellow 6),
(11) 4-[4,5-dihydro-3-methyl-5-oxygen-4-(phenylazo)-1H-pyrazol-1-yl]-benzenesulfonic acid, (common name (color index title): acid yellow 11),
(12) 4,4 '-[(3,3 '-dichloro [1,1 '-xenyl]-4,4 '-two bases) bisazo] two [2,4-dihydro-5-methyl-2-phenyl-3H-pyrrole is than azoles quinoline-3-ketone, (common name (color index title): pigment orange 13),
(13) azo 2-[(4-methoxyl group-2-nitrobenzophenone)]-N-(2-aminomethyl phenyl)-3-oxygen-butyramide, (common name (color index title): pigment orange 1),
(14) 3,3 '-[(2,5-dimethyl-1,4-phenylene) two [imino group (1-acetyl group-2-oxygen-2,1-ethane two bases) azos]] two [4-chloro-N-(5-chloro-2-aminomethyl phenyl)-Benzoylamide, (common name (color index title): pigment yellow 95),
(15) 3,3 '-[(2,5-dimethyl-1,4-phenylene) two [imino group (1-acetyl group-2-oxygen-2,1-ethane two bases) azos]] two [4-chloro-N-(2, the 5-Dichlorobenzene base)-Benzoylamide, (common name (color index title): pigment yellow 166),
(16) 3,3 '-[(2-chloro-5-methyl isophthalic acid, 4-phenylene) two [imino group (1-acetyl group-2-oxygen-2,1-ethane two bases) azos]] two [4-chloro-N-(3-chloro-2-aminomethyl phenyl)-Benzoylamide, (common name (color index title): pigment yellow 93),
(17) 4,5-two chloro-2-[[4,5-dihydro-3-methyl-5-oxygen-1-(3-sulfonyl-phenyl)-1H-pyrrole is than azoles-4-yl] azo]-benzenesulfonic acid,
(18) 3,3 '-(1,4-phenylene diimino) two [4,5,6, the 7-tetrachloro]-1H-1-isoindolinones, (common name (color index title): pigment yellow 110),
(19) 3,3 '-[(2-methyl isophthalic acid, 3-phenylene) diimino] two [4,5,6, the 7-tetrachloro]-1H-1-isoindolinones, (common name (color index title): pigment yellow 109),
(20) 4,5,6,7-tetrachloro-3-[[3-methyl-4-[[4-[(4,5,6,7-tetrachloro-1-oxygen-1H-iso-indoles-3-yl) amino] phenyl] azo] phenyl] amino]-the 1H-1-isoindolinone, (common name (color index title): pigment orange 61),
(21) 3; 3 '-[(2-chloro-5-methyl isophthalic acid, 4-phenylene) two [imino group (1-acetyl group-2-oxygen-2,1-ethane two bases) azos]] two [4-chloro-N-[2-(4-chlorophenoxy)-5-(trifluoromethyl) phenyl]-Benzoylamides; (common name (color index title): pigment Yellow 12 8)
(22) 2,2 '-[1,4-phenylene two [imino group (1-acetyl group-2-oxygen-2,1-ethane two bases) azo]] is two-1,4-benzene dicarboxylic acid tetramethyl ester, (common name (color index title): pigment yellow 155),
(23) 3,3 '-[(2,5-two chloro-1,4-phenylene) diimino] is two-the 1H-1-isoindolinone, (common name (color index title): pigment yellow 17 3),
(24) 1,1 '-[(6-phenyl-1,3,5-triazines-2,4-two bases) diimino] is two-9, the 10-amerantrone, (common name (color index title): pigment yellow 147),
(25) 2,2 '-[1,2-ethane two base two (oxygen-2,1-phenylene azo)] two [N-(2,3-dihydro-2-oxygen-1H-benzimidazole-5-yl)-3-oxygen-butyramide, (common name (color index title): pigment yellow 180),
(26) N-[4-(amino carbonyl) phenyl]-4-[[1-[[(2,3-dihydro-2-oxygen-1H-benzimidazole-5-yl) amino] carbonyl]-2-oxygen propyl group] azo]-Benzoylamide, (common name (color index title): pigment yellow 181),
(27) chemical compound of following formula (I) representative:
[Chemical formula 1]
R wherein
1, R
2And R
3Identical or different, and represent hydrogen atom or alkali metal atom respectively.The example of alkali metal atom comprises lithium atom, sodium atom, potassium atom, rubidium atom etc.R wherein preferably in the chemical compound of formula (I) representative
1, R
2And R
3Identical or different, and represent the chemical compound of formula (I) representative of hydrogen atom, sodium atom or potassium atom respectively.R wherein more preferably
1, R
2And R
3Identical and the chemical compound of formula (I) representative of represent sodium atom respectively.
(28) chemical compound of following formula (II) representative:
[Chemical formula 2]
R wherein
4And R
5Identical or different, and represent hydrogen atom or alkali metal atom respectively.The example of alkali metal atom comprises lithium atom, sodium atom, potassium atom, rubidium atom etc.R wherein preferably in the chemical compound of formula (II) representative
4And R
5Identical or different, and represent the chemical compound of formula (II) representative of hydrogen atom, sodium atom or potassium atom respectively.R wherein more preferably
4And R
5Identical and the chemical compound of formula (II) representative of represent sodium atom respectively.
The chemical compound of above-mentioned (1)-(26) can use by salt form.The object lesson of salt form chemical compound comprises following compounds:
(1-a) 4-[[3-[(3,5-dimethylphenyl) azo]-2, the 4-dihydroxy phenyl] azo]-benzenesulfonic acid list sodium salt, (common name (color index title): acid orange 24),
(2-a) 2-(1,3-dioxy indane-2-yl)-quinoline disulfonic acid sodium salt, (common name (color index title): quinoline yellow),
(6-a) 5-chloro-2-[4,5-dihydro-3-methyl-4-[[4-[[(4-aminomethyl phenyl) sulfonyl] oxygen] phenyl] azo]-5-oxygen-1H-pyrazol-1-yl]-the benzenesulfonic acid sodium salt, (common name (color index title): Indian yellow 40),
(7-a) 8-hydroxyl-5,7-dinitro-2-LOMAR PWA EINECS 246-676-2 disodium salt, 4-[4,5-dihydro-3-methyl-5-oxygen-4-(phenylazo)-1H-pyrazol-1-yl]-the benzenesulfonic acid sodium salt, (common name (color index title): Indian yellow 1) and
(17-a) 4,5-two chloro-2-[[4,5-dihydro-3-methyl-5-oxygen-1-(3-sulfonyl-phenyl)-1H-pyrazoles-4-yl] azo]-benzenesulfonic acid calcium salt (1: 1), (common name (color index title): pigment yellow 183),
Chemical compound (1)-(28) and salt thereof can metallic lakes form use.The example that is used for the metal of this metallic lakes comprises barium, zirconium, calcium, magnesium, aluminum etc.
As the material that intercepts the light in the 365nm-430nm wave-length coverage, chemical compound (1)-(28) and salt thereof can be used singly or in combination.
Chemical compound (1)-(28) are known, and these chemical compounds can prepare by known method in addition, and can be purchased.
The object lesson that the material that intercepts light in the 365nm-430nm wave-length coverage is added the method in the packing container comprises: a kind of method that comprises the steps, the material that intercepts light in the 365nm-430nm wave-length coverage is mediated with suitable amount in the base material of packing container, and preparation comprises the packing container of this material thus; A kind of material that will intercept light in the 365nm-430nm wave-length coverage is applied to method on the ready-made packing container with suitable amount; And a kind of usefulness comprises the method that film that appropriate amount intercepts the material of light in the 365nm-430nm wave-length coverage covers ready-made packing container.The example that this film is applied to a preferred embodiment of the method on the container comprises: a kind of method that comprises the steps, the heat shrink films that will comprise the material of light in the appropriate amount obstruct 365nm-430nm wave-length coverage is applied on the packing container, heat the gained container then so that film sticks on the packing container, the packing container with this film coating is provided.
When being used for packing container of the present invention is to mediate when forming into the packing container material by the material that will intercept light in the 365nm-430nm wave-length coverage, and the content of this material waits suitably according to the form of photoresistance parting matter and packing container type of material, packing container and determines in the packing container material.For example, under the situation of the about 1mm of about 0.1mm-, the ratio of photoresistance parting matter is 0.001-15 weight % at the thickness of packing container, preferred 0.001-10 weight %, and more preferably 0.01-5 weight % is based on the total amount of packing container material.
In the time will being applied on the packing container with the film that the material that intercepts light in the 365nm-430nm wave-length coverage is mediated, the content of photoresistance parting matter in film changes according to the form of the type of the type of photoresistance parting matter, film and thickness, packing container etc.The toatl proportion of photoresistance parting matter for example is 0.0001-15 weight %, preferred 0.001-10 weight %, more preferably 0.01-5 weight %.
In addition, under the situation of using chemical compound (1)-(28), preferably these chemical compounds are present in wherein visible (transparent) packing container top surface area 1cm of content
2Part, and total amount of compound is 0.001mg-20mg, preferred 0.01mg-5mg, and more preferably 0.1mg-1mg.
The base material of packing container of the present invention is also unrestricted, can be glass, plastics, cellulose, pulp (pulp), rubber etc.When holding aqueous formulation, preferred plastic containers are as packing container, and this is in view of its squeezable character and durability.
Preferred thermoplastic resin is as the resin that is used for plastic packaging containers of the present invention, and the example of thermoplastic resin comprises the resin based on alkene; Resin based on polyester; Resin based on polyphenylene oxide; Resin based on Merlon; Resin based on polysulfones; Resin based on polyamide; The rigid polyvinyl chloride resin; The resin of styrene-based etc.When packing container was plastic containers, the preferred use had good extrudability matter and the resin of durability to stand to oppress repeatedly.
In addition, in conjunction with effect of the present invention, being used for packing container of the present invention can be by adding UV absorbent, infrared absorbent etc. at resin, perhaps be applied to resin surface by the smears that will comprise these compositions and further improve the light stability of tranilast or its salt.
(ii) pharmaceutical preparation
In drug products according to the present invention, pharmaceutical preparation is accommodated in the above-mentioned packing container.
The tranilast that is included in the pharmaceutical preparation is meant (N-(3,4-dimethoxy cinnamoyl) ortho-aminobenzoic acid.
Replace above-mentioned tranilast or with its combination, the salt of tranilast can be used for being contained in the pharmaceutical preparation of packing container.To the salt of tranilast without limits, as long as this salt is acceptable on the materia medica.Its object lesson comprises inorganic salt such as sodium salt, potassium salt etc.; Salt with organic amine such as morpholine, piperazine, pyridine, pyrroles etc.; With amino acid whose salt etc.The salt of these tranilasts can be used alone or in combination.
In the present invention, for be contained in the packing container pharmaceutical preparation without limits, as long as wherein comprise tranilast and/or its salt.For example, pharmaceutical preparation can only comprise tranilast and/or its salt, or except tranilast and/or its salt, can comprise acceptable alkali on the materia medica, carrier, other medicines learn component, other additive etc.
In the present invention, according to the purpose purposes of pharmaceutical preparation, dosage form etc., suitably determine to be contained in the content of tranilast in the pharmaceutical preparation of packing container and/or its salt.For example, when oral drug preparation, suitably determine its daily dose as follows: the total amount of tranilast and salt thereof is adjusted in the scope of 50mg-500mg.Under the situation of local application pharmaceutical preparation, suitably determine its daily dose as follows: the total amount of tranilast and salt thereof is adjusted in the scope of 0.01mg-50mg.Specifically, under the situation of aqueous pharmaceutical preparations, with respect to the total amount of pharmaceutical preparation, the toatl proportion of tranilast and/or its salt is 0.01-20 weight %, preferred 0.01-10 weight %, and more preferably 0.1-5 weight %.
Be contained in pharmaceutical preparation in the packing container except (A) tranilast and/or its salt, can also further comprise (B) (B-1) berberine, its derivant or its salt (being referred to as " chemical compound (B-1) " hereinafter); (B-2) vitamin B2, its derivant or its salt (being referred to as " chemical compound (B-2) " hereinafter); (B-3) Hesperidin, its derivant or its salt (being referred to as " chemical compound (B-3) " hereinafter); (B-4) hydroxyquinoline, its derivant or its salt (being referred to as " chemical compound (B-4) " hereinafter); (B-5) vitamin B12, its derivant or its salt (being referred to as " chemical compound (B-5) " hereinafter).Hereinafter, these chemical compounds are collectively referred to as " chemical compound (B) ".These chemical compounds (B) can be used alone or in combination.In drug products of the present invention, add one or more these chemical compounds (B) and can further improve the tranilast that is included in the drug products of the present invention and/or the light stability of its salt.
The object lesson of chemical compound (B-1) comprises berberine, berberine tannate, berberine chloride, berberine sulfate etc.
The object lesson of chemical compound (B-2) comprises flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), riboflavin, cytoflavin, riboflavin acetas, Riboflavine Tertrabutyrate, its sodium salt etc.
The object lesson of chemical compound (B-3) comprises Hesperidin, hesperidin methyl etc.
The object lesson of chemical compound (B-4) comprises hydroxyquinoline, Hydroxyquinoline Sulfate, hydroxyquinoline phosphate etc.
The object lesson of chemical compound (B-5) comprises cobalamin, mecobalamin, cobamamide, hydroxocobalamin, its hydrochlorate, its acetate etc.
Being used for pharmaceutical preparation of the present invention can comprise at least a in chemical compound (1)-(28 of above mentioning about (i) part of packing container), as long as this chemical compound is that materia medica is acceptable, thereby during the compounding pharmaceutical preparation, also guarantee the light stability of tranilast or its salt.
If necessary, be used for pharmaceutical preparation of the present invention and can comprise solubilizing agent.Particularly when pharmaceutical preparation is formulated as aqueous pharmaceutical preparations, preferably be mixed with solubilizing agent therein.The solubilizing agent of mentioning has trometamol, monoethanolamine, diethanolamine, triethanolamine or similar organic amine; Polyvinyl pyrrolidone; Polysorbate or similar surfactant; Propylene glycol or similar polyhydroxy-alcohol; Caffeine or similar xanthine derivative; Or the like.Wherein polyvinyl pyrrolidone, caffeine, trometamol, monoethanolamine, diethanolamine and triethanolamine have the effect of the effect of enhancing above-claimed cpd (B), promptly improve the light stability of tranilast, and when above-claimed cpd (B) is included in the pharmaceutical preparation, be particularly preferred therefore.These solubilizing agents can be used alone or in combination.
Under the situation of aqueous pharmaceutical preparations, if wherein be mixed with solubilizing agent, its content 0.001-10 weight % normally for example then, preferred 0.05-10 weight %, and more preferably 0.1-5 weight % are based on the total amount of pharmaceutical preparation.
By being used for the specific non-ionic surface active agent of pharmaceutical preparation adding of the present invention, can more effectively improve the light stability of tranilast and salt thereof.The suitable example of non-ionic surface active agent comprises POE-POP block copolymer, POE sorbitan aliphatic ester, POE Oleum Ricini or POE hardened castor oil.Specifically, preferred POE (60) hardened castor oil, polysorbate 80 and POE-POP block copolymer 407.At this, the molal quantity that digitized representation added (average mol that is added) in the bracket, " POE " and " POP " is respectively the abbreviation of polyoxyethylene and polyoxypropylene.These non-ionic surface active agents can be used alone or in combination.
Under the situation of aqueous pharmaceutical preparations, the normally about 0.001-1 weight of the content of non-ionic surface active agent wherein %, preferably about 0.01-1 weight %, and 0.05-1 weight % more preferably from about are based on the total amount of pharmaceutical preparation.
When chelating agen further being mixed into when being used for pharmaceutical preparation of the present invention, can give the tranilast and the more excellent light stability of salt thereof that are included in the pharmaceutical preparation.The suitable example of this chelating agen comprises ethylenediaminetetraacetic acid, citric acid and salt thereof.Particularly preferably be ethylenediaminetetraacetic acid and salt thereof as chelating agen.Its object lesson comprises disodiumedetate, edta disodium dihydrate (sodium ethylene diamine tetracetate) etc.These chelating agen can be used alone or in combination.
When the total amount of tranilast and salt thereof was 1 weight portion, chelating agen content for example was the 0.0001-10 weight portion, preferred 0.001-10 weight portion, more preferably 0.001-1 weight portion, and preferred especially 0.01-1 weight portion.
When being used for pharmaceutical preparation of the present invention and being aqueous pharmaceutical preparations, in this pharmaceutical preparation, be mixed into specific buffer agent substitute chelating agen or with its combination, thereby give tranilast and the more excellent light stability of salt thereof that is included in the pharmaceutical preparation.The example of sort buffer agent comprises borate buffer, phosphate buffer, carbonate buffer agent etc.Wherein preferred boric acid salt buffer agent and phosphate buffer.If be mixed in the pharmaceutical preparation, then the ratio of buffer agent is generally 0.0001-10 weight %, preferred 0.001-5 weight %, and the about 3 weight % of more preferably 0.01-5 weight %, and especially preferably about 0.1-are according to the concentration of buffer agent total amount
When being used for pharmaceutical preparation of the present invention and being aqueous pharmaceutical preparations, its pH is adjusted in the scope of 4-9 usually.In order to keep the good light stability of tranilast and/or its salt, pH is preferably 6-8.5, more preferably 7-8.5, and preferred especially 7-8.Under the situation of aqueous pharmaceutical preparations, infiltration than be the ratio of Morie osmolarity and the Morie osmolarity of normal saline of pharmaceutical preparation usually in the scope of 0.3-4.1, preferably 0.3-2.1, and especially preferably about 0.5-about 1.4.
According to the purpose purposes, will be used for pharmaceutical preparation of the present invention and various carrier combinations is adjusted into various dosage forms, carrier such as aqueous carrier, hydrophilic carrier, oily carrier, liquid-carrier, powder/granule carrier etc.As the dosage form of pharmaceutical preparation of the present invention, can mention following various forms: tablet, powder, granule, capsule, dry syrup or similar solid dosage forms; Plaster, ointment, cream or similar semisolid dosage form; With eye drop, nasal drop, washing liquid, leachate, suspension, emulsion, syrup, injection (injection that comprises preparation before using), aerosol, soft capsule, beverage or similar liquid dosage form etc.Be exposed to the unstability of light time in view of the present invention can prevent tranilast and/or its salt effectively, as the special preferred dosage form of pharmaceutical preparation of the present invention, what can mention is the aqueous dosage form.The example of this aqueous pharmaceutical preparations comprises aqueous liquid preparation and semi-solid preparation.
Preparation that be used for pharmaceutical preparation of the present invention and can be injection, suppository, medicinal preparation for oral administration, is used to suck etc. perhaps can be by the part of local application at health, and this body part is exposed to light during using.Pharmaceutical preparation of the present invention not only can be applied on the skin, and can be applied to stimulating (eye mucosa such as cornea, conjunctiva etc. on the responsive film; Gingiva; Tongue; Lip; Oral mucosa; Nasal mucosa; Pharyngolaryngeal mucosa etc.).The object lesson that is used for pharmaceutical preparation of the present invention comprises externally used paste, external-application cream, external use liquid or similar external skin care formulations; Eye drop; Collyrium; Spongaion; Contact lens wear liquid; Contact lens care agent (such as cleanout fluid, soak, disinfectant solution, multipurpose liquid etc.); Nasal drop; Irritate the nose fluid; The throat medicine; Collutory; Ear drop etc.Preferred eye drop, collyrium, injection, external skin care formulations, nasal drop and contact lens care agent in above-mentioned.
The present invention makes the pharmaceutical preparation that visualization with the naked eye is contained in the packing container from its outside become possibility, make can check foreign substance existence whether.Therefore, favourable part of the present invention is to be convenient to the quality control of pharmaceutical preparation, particularly such as eye drop, collyrium and injection.In addition, favourable part of the present invention is also that when the pharmaceutical preparation of two or more dosage is housed user can with the naked eye be checked the amount of remaining pharmaceutical preparation the packing container from its outside when each the use in packing container.Comprise eye drop, collyrium, external skin care formulations, nasal drop and contact lens care agent with pack into the example of the pharmaceutical preparation in the packing container of two or more dosage.
Be used for pharmaceutical preparation of the present invention and can comprise pharmacologic activity composition and/or bioactive ingredients, as long as effect of the present invention is not subjected to negative effect with mentioned component.
About drug products of the present invention, the amount that is contained in the pharmaceutical preparation in the packing container can suitably be determined according to the dosage number of the pharmaceutical preparation of the single dosage of pharmaceutical preparation, each packing container etc.
II. suppress photodegradative method
As mentioned above, allow user visualization content and obstruct wave-length coverage can suppress the light degradation of tranilast and salt thereof at the packing container of the light of 365nm-430nm.From another viewpoint different with foregoing, the invention provides a kind of be used to suppress tranilast and the photodegradative method of salt thereof, this method comprises that the pharmaceutical preparation that (i) contained tranilast and/or its salt is packed into and (ii) intercepts the packing container of wave-length coverage at the light of 365nm-430nm.
In the method for the invention, the type of employed tranilast and salt thereof, their content in pharmaceutical preparation, be mixed into other composition in the pharmaceutical preparation, pharmaceutical preparation form, intercept wave-length coverage at the packing container of the light of 365nm-430nm to use with the identical mode of pharmaceutical preparation in the packing container that is contained in mentioned above.
Embodiment
Hereinafter, describe the present invention in further detail, but be not limited to embodiment with reference to embodiment.
Test implementation example 1: suppress the affirmation test of tranilast degraded
Preparation has the pharmaceutical preparation that contains tranilast of prescription shown in the table 1 (prescription 1), and passes through the film filter filtration of 0.2 μ m subsequently.The pharmaceutical preparation that will contain tranilast then is assigned in some 10ml containers of being made by the various materials shown in the table 2 with the component of 10ml, and subsequently with seal of vessel.With obtain thus be contained in the container each contain tranilast pharmaceutical preparation with the light stability test device with (room temperature) continuous irradiation 60 hours under 25 ℃ of the light of 5000 luxs, therefore the accumulation light of preparation exposes as 300000 luxs hour, wherein the light stability test set comprises that the D65 fluorescent lamp is as light source (trade name " Light-Tron LT-120 D3CJ type, the product of Nagano Science and Technology Ltd.).After this, each contains the tranilast concentration of tranilast pharmaceutical preparation by high-performance liquid chromatography analysis, thereby determines the residual concentration of tranilast.Based on the residual concentration of measured tranilast calculate the residue tranilast with respect to photoirradiation before the ratio (%) of tranilast concentration.For the light transmittance of estimating the container that is used for this test and being applied to the various films on the container, container and film are cut into the tabular sampling.Spectral transmission meter by common employing lens TM-1 (product of TOPCON) is estimated these samples, to determine the light transmittance (seeing Fig. 1-11) in the wave-length coverage 280nm-800nm.Determine the average transmittance of wave-length coverage 365nm-430nm, 350nm-430nm and 350nm-450nm thus.
This test uses glass, polypropylene (PP) and polyethylene terephthalate (PET) container to carry out.Every means, this test is used to be coated with the container of various films and to be mixed with brown or yellow-viridine green and is carried out (seeing Table 2) with painted container as photoresistance.In a usual manner shrink film (heat shrink films) is administered to the whole outside of container, and the film of other type is wrapped in the whole exterior circumferential of container, fix with adhesive tape then.The film that is used for this test obtains as follows: red membrane (TOYO company, red glass paper); Yellow film (TOYO company, yellow glass paper); Green film (TOYO company, green glass paper); Blue film (TOYO company, blue tinted glass paper); With reddish violet film (purple glass paper).
The content observability that is used for the container of this test according to following evaluation criterion evaluation:
＜evaluation criterion 〉
Whether the amount of ◎ interior contents and the existence of foreign substance can clearly be visually observed;
Whether the amount of zero interior contents and the existence of foreign substance can be visually observed;
The amount of △ interior contents can be visually observed, but whether the existence of foreign substance can not be visually observed;
The amount of * interior contents can not be visually observed.
Table 1
| Composition (g/100mL) | Prescription 1 |
| Tranilast | 0.5 |
| Polyvinyl pyrrolidone | 3.0 |
| Boric acid | 1.3 |
| Borax | 0.7 |
| Polysorbate 80 | 0.1 |
| Hydrochloric acid | In right amount |
| Sodium hydroxide | In right amount |
| Benzene Chloride first hydroxylammonium | 0.005 |
| Purified water | In right amount |
| Total amount | 100ml |
| pH | 7.5 |
| The infiltration ratio | 1 |
By being set at 1 and calculating the infiltration ratio with defined in the osmotic pressure of normal saline such as the Japanese Pharmacopoeia.
Be used for the container of this test, wave-length coverage 455nm-780nm have 30% or the container of higher average transmittance be fully transparent so that the pharmaceutical preparation of wherein holding can be visually observed from the outside, and therefore preferably as container of the present invention.In addition, be used for the container of this test, be coated with the container of redness, yellow or green film and Huang-green pet container and show 30% or higher average transmittance, and they intercept the light (see Fig. 1-4 and table 2) of wave-length coverage at 365nm-430nm effectively at wave-length coverage 455nm-780nm.
Table 2 is also expressed the measurement result of tranilast residual rate after the rayed.As can be seen from Table 2, being contained in every kind of intercepting in the container of light that wave-length coverage is 365nm-430nm contains tranilast pharmaceutical preparation show obviously high tranilast residual concentration after rayed.It is not only low in wave-length coverage 365nm-430nm that this has confirmed that also tranilast is contained in average transmittance with being stabilized, and in wave-length coverage 350nm-450nm and 350nm-430nm in the low container.On the contrary, confirmed to be contained in containing in the tranilast pharmaceutical preparation in those containers that average transmittance is high in wave-length coverage 365nm-430nm, the tranilast degraded that is caused by rayed is not suppressed.
The above results shows that the light in the wave-length coverage 365nm-430nm causes the degraded of tranilast when being exposed to the light time, and therefore suppresses to be exposed to the degraded of light time tranilast by intercepting light in this wave-length coverage.In addition, find that also the tranilast pharmaceutical preparation that contains be contained in the container guaranteed good content observability, this container has 30% or higher average transmittance at wave-length coverage 455nm-780nm.
[table 2]
| Container | Visual | Stability | |||||||
| Material (painted) | Use film | The average transmittance of the light of wave-length coverage 365nm-430nm (%) | The average transmittance of the light of wave-length coverage 350nm-430nm (%) | The average transmittance of the light of wave-length coverage 350nm-450nm (%) | The average transmittance of the light of wave-length coverage 455nm-780nm (%) | The evaluation of content visuality | The remaining proportion of tranilast (%) behind the photoirradiation of 300000 Ix | ||
| Embodiment | 1 | Glass | Red membrane | 1 | 1 | 1 | 48 | ○ | 96.2 |
| 2 | Glass | Yellow film | 1 | 1 | 1 | 78 | ◎ | 93.4 | |
| 3 | PP | Yellow film | 1 | 1 | 1 | 78 | ◎ | 94.1 | |
| 4 | PP | Yellow shrink film | 3 | 2 | 3 | 75 | ◎ | 93.5 | |
| 5 | | Green film | 0 | 1 | 1 | 42 | ○ | 95.2 | |
| 6 | PET (yellow green) | 1 | 1 | 4 | 79 | ◎ | 96.1 | ||
| Comparative Examples | 1 | Glass | - | 90 | 90 | 90 | 92 | ◎ | 9.8 |
| 2 | PP | - | 89 | 90 | 89 | 91 | ◎ | 8.2 | |
| 3 | Glass | The reddish violet film | 69 | 68 | 67 | 66 | ◎ | 23.8 | |
| 4 | Glass | Blue film | 48 | 44 | 45 | 30 | ○ | 42.8 | |
| 5 | Glass | Blue film (2) | Undetermined | 18 | 18 | 19 | △ | 77.9 | |
| 6 | Glass | Blue film (3) | 10 | 9 | 9 | 16 | △ | 93 | |
| 7 | PP (brown) | - | 36 | 36 | 35 | 56 | ○ | 33.3 | |
In the table 2, film is not used in labelling "-" expression in " using film " hurdle.In " using film " hurdle, " blue film (2) " expression is administered to two blue film on the container, and " blue film (3) " expression is administered to three blue film on the container.
Test implementation example 2
Preparation has the pharmaceutical preparation that contains tranilast of prescription shown in the table 1 (prescription 1), and passes through the film filter filtration of 0.2 μ m subsequently.
Preparation is respectively: aqueous solution (specimen A) comprises the chemical compound that 0.01 weight % formula (I) is represented, wherein R
1, R
2And R
3Difference represent sodium atom; Aqueous solution (specimen B) comprises the chemical compound that 0.1 weight % formula (I) is represented, wherein R
1, R
2And R
3Difference represent sodium atom; Aqueous solution (specimen C) comprises the chemical compound that 0.01 weight % formula (II) is represented, wherein R
4And R
5Difference represent sodium atom; And aqueous solution (specimen D), comprise the chemical compound that 0.1 weight % formula (II) is represented, wherein R
4And R
5Difference represent sodium atom.
The as above prepared pharmaceutical preparation that contains tranilast is assigned to (external diameter 25mm in some 10ml nut bottles with the component of 10ml, trade name " SV-10 ", the product of NICHIDEN-RIKA Glass Co., Ltd.), and, prepare some gas-tight containers that contain tranilast pharmaceutical preparation that hold with described bottle sealing.Subsequently each is held the gas-tight container that contains tranilast pharmaceutical preparation be placed in the 50ml nut bottle (internal diameter 35mm, trade name " SV-50 ", the product of NICHIDEN-RIKA Glass Co., Ltd.).One of as above prepared specimen A-D is joined in each 50ml nut bottle until heap(ed) capacity, surround by this way and hold the gas-tight container (embodiment 7-10) that contains tranilast pharmaceutical preparation.Use the 50ml nut bottle that holds pharmaceutical preparation of preparation thus to carry out following test as the model that contains tranilast pharmaceutical preparation that is contained in the packing container.Contain tranilast pharmaceutical preparation for being contained in as each of test model in the packing container, the existence that contains the amount of tranilast pharmaceutical preparation and foreign substance from the outside visualization of packing container whether.
With above-mentioned each 50ml nut bottle (embodiment 7-10) that holds pharmaceutical preparation with (room temperature) continuous irradiation 60 hours under 25 ℃ of the light of 5000 luxs, wherein the light stability test set comprises that the D65 fluorescent lamp is as light source (trade name " Light-Tron LT-120 D3CJ type ", the product of Nagano Science and Technology Ltd.), thus each accumulation light that contains tranilast pharmaceutical preparation expose as 300000 luxs hour.After this, each contains tranilast pharmaceutical preparation and stands high speed liquid chromatography, thereby determines the residual concentration of tranilast.Based on measured tranilast residual concentration calculate tranilast with respect to photoirradiation before the residue ratio (%) of tranilast concentration.
In order to compare, the aqueous specimen of test pack (Comparative Examples 8) similarly.
Table 3 illustrates the result.The result shows that the optics that has suppressed tranilast significantly decomposes when the pharmaceutical preparation that contains tranilast when by formula (I) or (II) chemical compound of representative covers.
Table 3
| Employed specimen | The residue ratio of tranilast | |
| Embodiment 7 | Specimen A:[aqueous solution comprises the chemical compound that 0.01 weight % formula (I) is represented, wherein R 1、R 2And R 3Difference represent sodium atom] | 90.6 |
| Embodiment | ||
| 8 | Specimen B:[aqueous solution comprises the chemical compound that 0.1 weight % formula (I) is represented, wherein R 1、R 2And R 3Difference represent sodium atom] | 98.2％ |
| Embodiment 9 | Specimen C:[aqueous solution comprises the chemical compound that 0.01 weight % formula (II) is represented, wherein R 4And R 5Difference represent sodium atom] | 81.3 |
| Embodiment | ||
| 10 | Specimen D:[aqueous solution comprises the chemical compound that 0.1 weight % formula (II) is represented, wherein R 4And R 5Difference represent sodium atom] | 97.8％ |
| Comparative Examples 8 | Water | 10.2％ |
Industrial applicability
The invention provides a kind of drug products, the pharmaceutical preparation that wherein comprises tranilast and/or its salt is accommodated in the packing container of guaranteeing its content observability. In this drug products, the pharmaceutical preparation that is contained in the packing container can observe with the naked eye, and further, has significantly suppressed owing to light exposes the tranilast degraded that causes. Therefore according to the present invention, can be more reliable so that contain production process control and the quality control of pharmaceutical preparation of tranilast and/or its salt, and can improve the storage stability that contains the tranilast pharmaceutical preparation.
Be used for suppressing tranilast and the photodegradative method of salt thereof according to the present invention, only be placed on the light that intercepts particular range of wavelengths by the pharmaceutical preparation that will contain tranilast and/or its salt and guarantee in the packing container of its content observability, just can significantly suppress the light degradation of tranilast and/or its salt. Therefore the method according to this invention can suppress the light degradation of tranilast and salt thereof, and the existence that can with the naked eye estimate in addition the amount, state of the pharmaceutical preparation in the packing container and insoluble foreign substance whether. Therefore, the present invention can be so that contain quality control in the tranilast pharmaceutical preparation production process. In addition, the favourable part that is obtained by method of the present invention, be contained in the pharmaceutical preparation in the packing container is, the user can be before use with the naked eye from amount and the state of packing container visual examination content.
Claims (13)
1. a drug products is included at least a component pharmaceutical formulation that is selected from tranilast and salt thereof that contains in the packing container, and it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
2. according to the drug products of claim 1, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm.
3. according to the drug products of claim 2, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-430nm.
4. according to the drug products of claim 2, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 350nm-450nm.
5. according to the drug products of claim 1, wherein said packing container is 20% or lower at the average transmittance of wave-length coverage 365nm-430nm, at wave-length coverage 350nm-430nm is 20% or lower, and is 20% or lower at wave-length coverage 350nm-430nm.
6. according to the drug products of claim 1, wherein said packing container is 30% or higher at the average transmittance of wave-length coverage 455nm-780nm.
7. according to the drug products of claim 1, wherein said pharmaceutical preparation also comprises at least a following component that is selected from: berberine, vitamin B2, Hesperidin, hydroxyquinoline, vitamin B12, their derivant and their salt.
8. according to the drug products of claim 1, wherein said pharmaceutical preparation is aqueous formulation.
9. drug products according to Claim 8, wherein the amount toatl proportion of tranilast and salt thereof is 0.01-20 weight %, based on the total amount of pharmaceutical preparation.
10. according to the drug products of claim 1, wherein said pharmaceutical preparation is eye drop, collyrium, injection, external skin medicament, nasal drop or contact lenses nursing agent.
11. one kind is used to suppress tranilast or the photodegradative method of its salt, comprise that will contain at least a component pharmaceutical formulation that is selected from tranilast and salt thereof places packing container, it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
12. packing container is used to suppress at least a component that is selected from tranilast and salt thereof in the purposes that is exposed to the light time degraded, it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
13. packing container is used to prevent to contain at least a component pharmaceutical formulation that is selected from tranilast and salt thereof in the purposes that is exposed to the light time degraded, it is visible seeing through described container contents, and described container intercepts the light of wave-length coverage at 365nm-430nm.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004098542A JP5477996B2 (en) | 2003-09-30 | 2004-03-30 | Pharmaceutical preparation containing tranilast in transparent packaging |
| JP098542/2004 | 2004-03-30 | ||
| JP107022/2004 | 2004-03-31 | ||
| JP107023/2004 | 2004-03-31 | ||
| JP120771/2004 | 2004-04-15 | ||
| JP120772/2004 | 2004-04-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1938011A true CN1938011A (en) | 2007-03-28 |
Family
ID=37955101
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200580010121 Pending CN1938011A (en) | 2004-03-30 | 2005-03-29 | Pharmaceutical product containing tranilast |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1938011A (en) |
-
2005
- 2005-03-29 CN CN 200580010121 patent/CN1938011A/en active Pending
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