CN109303762A - Semisolid preparation and preparation method thereof containing Ketoprofen - Google Patents
Semisolid preparation and preparation method thereof containing Ketoprofen Download PDFInfo
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- CN109303762A CN109303762A CN201810842051.7A CN201810842051A CN109303762A CN 109303762 A CN109303762 A CN 109303762A CN 201810842051 A CN201810842051 A CN 201810842051A CN 109303762 A CN109303762 A CN 109303762A
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- semisolid preparation
- ketoprofen
- semisolid
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- essential oil
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
An aspect of of the present present invention provides semisolid preparation and preparation method thereof, the semisolid preparation is the semisolid preparation comprising Ketoprofen and gelling agent, and the semisolid preparation includes the ethyl alcohol of the solvent as Ketoprofen of 25~35 weight % and includes physiologically compatible alkanolamine in such a way that pH is 6.0~6.5.
Description
Technical field
The present invention relates to semisolid preparation of the Ketoprofen as principal component is contained, more specifically, relate to ensure to lead
The transdermal rate of the ageing stability of ingredient and property stability and improved principal component with preparation contains ketone
Semisolid preparation of ibuprofen and preparation method thereof.
Background technique
The analgesic agent of the arylpropionic acids structure such as brufen, naproxen or Ketoprofen is due to ease of use and stability
And the semisolid medicaments of gel or emulsifiable paste etc are made, for local treatments such as the Pain managements such as courbature and antiinflammations
It is widely used.
The carbopol gel of arylpropionic acid can be by that will make it dissolve using free acid principal component as initial substance in second
The aqueous dispersions of carboxyl vinyl polymer are added in the solution by the appropriate solvent of alcohol etc, finally use triethanolamine, diethanol
The physiologically compatible amine compounds of amine or tromethamine etc are neutralized, thus gel needed for preparation.Above-mentioned carboxylic
Base polyvinyl plays a role as the gelling agent for being used to prepare above-mentioned gel, in order to increase the viscosity of gel, suitable
Gelatine occurs sharply, should be neutralized with alkali, and above-mentioned alkali needs to neutralize gelling agent and principal component can.For
Physiologically compatible alkanolamine, such as triethanolamine, diethanol amine or tromethamine can be used in the neutralizer for stating neutralization.
However, using triethanolamine or diethanol amine as above-mentioned alkanolamine and according to the above method with about 1 to 3 weight %
Concentration preparation ketoprofen gel have Ketoprofen with as neutralizer alkanolamine precipitate in a salt form and principal component analyse
Tendency out.The often precipitating as more obvious appearance at 20 DEG C of temperature below for being equivalent to common preservation condition.
Above-mentioned precipitating declines the property stability of semisolid preparation, and thus the transdermal rate of principal component reduces and may induce drug effect
Decline.
Delivered for prevent when preparing this ketoprofen gel because with due to amine neutralizer forming salt principal component be precipitated
The semisolid preparation (patent document 1) of phenomenon.Above-mentioned semisolid preparation is described to make by using dexketoprofen trometamol
For Ketoprofen, the phenomenon that so as to overcome principal component to be precipitated.However, not yet developing as having improved stabilization in the present invention
The semisolid preparation of property and percutaneous permeability.
[existing technical literature]
[patent document]
(patent document 1): Korean granted patent 0543558
Summary of the invention
Technical problem
An aspect of of the present present invention the precipitation for not occurring principal component is provided and the property stability of preparation is high, can ensure it is main at
The semisolid preparation containing Ketoprofen of the ageing stability and the transdermal rate with improved principal component that divide.
Another aspect of the present invention provides the preparation method of the above-mentioned semisolid preparation containing Ketoprofen.
Technical solution
An aspect of of the present present invention provides a kind of semisolid preparation, and the semisolid preparation is comprising Ketoprofen and gelling agent
Semisolid preparation, the semisolid preparation contain the ethyl alcohol of the solvent as Ketoprofen of 25~35 weight % and with pH
6.0~6.5 mode contains physiologically compatible alkanolamine.
Another aspect of the present invention provides a kind of preparation method of the semisolid preparation of the one side of aforementioned present invention, packet
It includes following steps: the aqueous dispersions of carboxyl vinyl polymer is mixed to simultaneously homogeneous with the ethanol solution containing Ketoprofen and essential oil
Change；And by being added in resulting mixture in physiologically compatible alkanolamine progress and pH is adjusted to 6.0
~6.5 and form gel.
Beneficial effect
It has confirmed that, the semisolid preparation containing Ketoprofen of an aspect of of the present present invention does not occur in long-term preservation
The precipitation of the principal component and production quantity of impurity is significantly low, so as to ensure simultaneously preparation property stability and principal component it is steady
It is qualitative.In addition, above-mentioned semisolid preparation can be used as effectively containing since the transdermal rate of principal component significantly improves
There is the semisolid preparation of Ketoprofen.
Detailed description of the invention
Fig. 1 is the process flow chart of the preparation method of the semisolid preparation containing Ketoprofen of one embodiment of the invention.
Fig. 2 is that pH and viscosity are measured by object of the gel of Examples 1 to 5 and comparative example 1~7, takes appropriate (about 200mg)
It is applied to the photo of character when shooting was using 1 minute after skin.
Fig. 3 is meat after placing 1 month under the conditions of 25 DEG C, 60%RH by object of the gel of embodiment 1 and Comparative Examples 1 and 2
Eye is observed and shoots the photo of character in actual use.
Fig. 4 is ketoprofen gel of the display for embodiment 1,4,5 and comparative example 5,6,7, with reference to British Pharmacopoeia (BP)
" Ketoprofen Gel (ketoprofen gel) " impurity item measures (A) each impurity and (B) generated over time
The chart of the result of the amount of total impurities.
Fig. 5 is to illustrate the result institute that the test of transdermal rate is carried out using the gel of embodiment 1,3,5 and comparative example 3,4
The chart of the transdermal rate of the principal component of measurement.
Specific embodiment
As long as all technical terms used in the present invention are not additionally carried out definition, with related fields of the invention
The identical meaning of the middle normally understood meaning of those of ordinary skill uses.Although in addition, describing preferred side in this specification
Method or sample, but the substance similar or equivalent with it is also contained in scope of the invention.In addition, what pass was recorded in this manual
Numerical value is also considered as the meaning comprising " about " even if indefinite point out.All publications recorded as a reference in this specification
Content be integrally incorporated by reference this specification.
An aspect of of the present present invention provides a kind of semisolid preparation comprising Ketoprofen and gelling agent, the semisolid preparation packet
The ethyl alcohol of the solvent as Ketoprofen containing 25~35 weight % and in such a way that pH is 6.0~6.5 comprising physiologically can phase
The alkanolamine of appearance.
In one concrete example, semisolid preparation can be by mixing water dispersant and Ketoprofen containing gelling agent in water
Ethanol solution after, physiologically compatible alkanolamine is added and is prepared so that pH is adjusted to 6.0~6.5 and forms gel.
Above-mentioned Ketoprofen, and can be with due to that can exist in the form of mirror image isomer in chemical structure there are chiral carbon
Exist in the form of excellent S (+)-enantiomer (dexketoprofen) of racemic mixture or pharmacological activity.In one concrete example,
Above-mentioned Ketoprofen is dexketoprofen.
In addition, above-mentioned Ketoprofen can exist in the form of pharmaceutically acceptable salt in a concrete example.Above-mentioned pharmacy
Upper acceptable salt refers to nontoxicity and is suitble to that any salt of semisolid preparation is made.Above-mentioned pharmaceutically acceptable salt has ketone
Ibuprofen lysine salt, but it is not limited to this.In another concrete example, above-mentioned Ketoprofen can be free Ketoprofen.
Term " Ketoprofen " in this specification should be interpreted as including the racemic mixture of Ketoprofen, dextrorotation ketone Lip river
It is fragrant, they pharmaceutically acceptable salt whole.
Any gelling agent that can prepare the semisolid preparation containing Ketoprofen, such as carboxyl can be used in above-mentioned gelling agent
Polyvinyl, methylcellulose, xanthan gum, diphenhydramine, methylcellulose, hydroxypropyl methyl cellulose (HPMC) or it
Any combination.In one concrete example, above-mentioned gelling agent is carboxyl vinyl polymer (for example, trade name Carbopol 941
(molecular weight about 1,250,000), carbomer 934 (molecular weight about 3,000,000), Acritamer 940 (molecular weight about 4,000,000)).Relative to combination
The total amount of object may include the carboxyl vinyl polymer of 0.5 to 3 weight %, can have according to usage amount different
Viscosity number.
The performance of compatible alkanolamine neutralizes above-mentioned gelling agent and the Ketoprofen as principal component in the above physiological
Effect, neutralization in this way, be capable of forming have about 5, the semisolid system of the viscosity sufficiently high of 000~60,000cps
Agent (such as gel).Term " physiologically compatible alkanolamine ", which refers to, makes above-mentioned gelling agent and as principal component in performance
It will not play the role of significant harmful alkanolamine while the effect that Ketoprofen neutralizes to human body.It can phase in the above physiological
The alkanolamine of appearance can be selected from the group being made of triethanolamine, diethanol amine, tromethamine and their any combination, but not
It is limited to this.
There is pH 6.0~6.5 due to above-mentioned alkanolamine, thus above-mentioned semisolid preparation does not occur the precipitation of principal component
And it is shown to maintain suitable viscosity and transparent character (referring to test example 1 and 2).
In one concrete example, above-mentioned semisolid preparation can have about 5,000~60,000cps.Above-mentioned model is being not achieved
In the case where enclosing, viscosity is too low and may trickle, and in the case where excessively, there are under the decline of the absorptivity of principal component or smear
The worry of drop.
In a concrete example, for above-mentioned semisolid preparation, 1.0 to 3.0 weights are used as carboxyl vinyl polymer
The triethanolamine of 3.0 to 4.0 weight % can be used as alkanolamine in the Acritamer 940 of amount %.Have so as to realize
The semisolid preparation that the viscosity and pH of about 5,000~60,000cps is 6.0~6.5.
Above-mentioned semisolid preparation can by using 1.0~2.0 weight %, more preferred with 1.3~1.7 weight %'s
Acritamer 940, and use the triethanolamine of 3.0~3.5 weight % as alkanolamine, to realize pH 6.0~6.5 and have
The content ratio of the semisolid preparation of 10,000~20,000cPs viscosity, above-mentioned carbomer and alkanolamine can according to gelling agent and
The specific type of alkanolamine and it is different, therefore be not limited to this.
Ethyl alcohol contained by above-mentioned semisolid preparation is the solvent as Ketoprofen and uses, total relative to semisolid preparation
Weight can contain 25~35 weight %, can specifically contain 27~33 weight %, can more specifically contain 30~33 weights
Measure %.Test result is shown, in the pH disengaging 6.0~6.5 of above-mentioned semisolid preparation or the content of ethyl alcohol relative to semisolid
In the case that total formulation weight is more than 35 weight %, the production quantity of impurity is significantly improved.Meet as a result, in above-mentioned semisolid preparation
In the case where 25~35 weight % the two of pH 6.0~6.5 and ethanol content, the miscellaneous of the Ketoprofen as principal component is confirmed
The significant ageing stability that is low and can ensuring principal component of the generation degree of matter (referring to test example 3).
In one concrete example, above-mentioned alkanolamine is triethanolamine.
In a concrete example, the semisolid preparation can also be comprising oil, and specifically, the oil can be essential oil.
In the present specification, term " essential oil (essential oil) " refers to having as the stem, leaf, root from plant
It the volatility of the origin of the smell issued in stem, bark, fruit, bud, resin etc. and can be discharged by steam distillation
The oil component lighter than water, also referred to as plants essential oil.As long as the essential oil being capable of such as gel, emulsifiable paste suitable for pharmaceutical field
Topical formulations, then can be known any essential oil.In a concrete example, the essential oil can be the terpene comprising 50% or more
The oil of alkene or aromatic compound.For example, the essential oil can for lavender oil, neroli oil, rosemary oil, eucalyptus oil or they
Any mixture.It, can by the inclusion of containing 50% or more the terpenes or the oil of aromatic compound in a concrete example
With the significant transdermal rate for improving principal component.
In one concrete example, above-mentioned essential oil is the oil that neroli oil and lavender oil are mixed with 1:1 weight ratio.
In a concrete example, relative to the total amount of semisolid preparation, the semisolid preparation can contain 0.5~3.0 weight
Measure the essential oil of %.For example, the total amount relative to semisolid preparation, can contain the essential oil of 0.5~2.0 weight %.For example, opposite
In the total amount of semisolid preparation, the essential oil of 1.0~2.0 weight % can be contained.
Due to containing above-mentioned essential oil, can significantly improve above-mentioned comprising semisolid preparation of the Ketoprofen as principal component
The transdermal rate of principal component therefore there is improved drug effect, and the appearance, stability and preference of product can be increased
Property and fragrance.Test result is shown, in the pH disengaging 6.0~6.5 of above-mentioned semisolid preparation or the content of essential oil relative to half
In the case that solid pharmaceutical preparation total weight is less than 0.5 weight %, the transdermal rate of principal component significantly reduces (test example 4).In addition,
The case where using the total weight relative to semisolid preparation to be more than the essential oil, for example, essential oil of 3.5 weight % of 3 weight %
Under, in harsh stability test, confirm the tendency (test example 3) that unknown impuritie increases by 0.2% or more.In addition, making
Be more than with the total weight relative to semisolid preparation 3 weight % essential oil in the case where, in local application semisolid preparation, essence
The smell of oil is strong, Preference may be made to be deteriorated, and since essential oil is high compared to other excipient prices, with usage amount
Increase, economy may be decreased.
As a result, the content that above-mentioned semisolid preparation meets pH 6.0~6.5 and essential oil be 0.5~3.0 weight % this
In the case where the two, principal component is not precipitated and is able to maintain that the property stability of preparation, while the transdermal rate of principal component is high
And there can be improved drug effect.It is furthermore possible to also provide appearance, the semisolid system of Preference and fragrance with excellent product
Agent simultaneously reduces production cost.
In a concrete example, for above-mentioned semisolid preparation, relative to the total amount of composition, 1.0 to 3.0 weight of use
The carboxyl vinyl polymer for measuring %, as alkanolamine, the triethanolamine of 3.0 to 4.0 weight % of use.And also comprising oily, from
And the viscosity with about 5,000~60,000cps and pH may be implemented as 6.0~6.5 semisolid preparation.
Above-mentioned semisolid preparation can locally be applied to skin in the form of preparation is melted into gel or emulsifiable paste.
Effective well known Ketoprofen is any when above-mentioned semisolid preparation can be used for topical application in the art
Indication.In one concrete example, above-mentioned semisolid preparation can be used for easing pain or anti-inflammatory.
In one concrete example, above-mentioned semisolid preparation can contain the Ketoprofen 1 as principal component using on the basis of free acid
~5 weight %, more preferably 1~3 weight %.
About above-mentioned semisolid preparation, pharmaceutically acceptable additive can be further included in semisolid preparation.
For example, may include preservative agent or colorant etc., this can be suitable for selection by those of ordinary skill.
The present invention provides a kind of preparation method of the semisolid preparation of the one side of aforementioned present invention in another aspect,
Include the following steps: to mix the aqueous dispersions of carboxyl vinyl polymer with the ethanol solution containing Ketoprofen and essential oil and equal
Matter；And by being added in resulting mixture in physiologically compatible alkanolamine progress and pH to be adjusted to
6.0~6.5 and form gel.
The detailed content of the preparation method of above-mentioned semisolid preparation can be directly using the one side for aforementioned present invention
Semisolid preparation explanation.
The aqueous dispersions of above-mentioned carboxyl vinyl polymer can be by being cooled to 60 DEG C of purification after being heated to 90 DEG C
Carboxyl vinyl polymer is added in water, is allowed to homogenize at about 50~70 DEG C, to prepare aqueous dispersions.
Also can be used the above-mentioned ethanol solution containing Ketoprofen, but further additional essential oil and prepare containing Ketoprofen and
The ethanol solution of essential oil and use, can be prepared and being simply mixed.
Then, the ethanol solution of Ketoprofen is added in the aqueous dispersions of above-mentioned carboxyl vinyl polymer or contains ketone Lip river
Fragrant and essential oil ethanol solution, is allowed to homogenize at 25~35 DEG C, and after implementing the step, physiologically compatible alkane is added
Hydramine is neutralized so that pH is adjusted to 6.0~6.5 and forms gel.
Being formed by gel can be by removing air under mild vacuum atmosphere, so that it is guaranteed that by oxygen in long-term preservation
The uniformity of the decline of stability caused by changing and vessel filling quality.
[embodiment]
Hereinafter, the present invention is described in more detail according to following embodiments.But following embodiments are only used for illustrating the present invention, this
The range of invention is not limited by this.
Embodiment 1-5: the preparation of semisolid preparation
According to the formula of following table 1, the ketoprofen gel of embodiment 1-5 is prepared.
Specifically, purified water is heated to be cooled to 60 DEG C after 90 DEG C, Acritamer 940 is added, carries out 30 points at 60 DEG C
Clock homogenizes, and the mixture that Ketoprofen and essential oil are dissolved in ethyl alcohol and formed then is added, in 30 DEG C of progress, 30 minutes homogeneous
Change, triethanolamine then is added while carrying out and homogenizing for 120 minutes for 30 DEG C on one side in carrying out and to form gel.It is right
In the gel of acquisition, air is removed under mild vacuum atmosphere.The process flow of this preparation method is illustrated in Fig. 1.
[table 1]
Comparative example 1-7: the preparation of semisolid preparation
Ketoprofen is prepared by mode identical with the preparation method of above-described embodiment 1-5 according to the formula of following table 2
Gel.
[table 2]
Test example 1: character confirms when the pH that is respectively formulated, viscosity and use based on pH
The gel of preparation is measured according to Pharmacopoeia Coreana routine test method pH measuring method using Orion 3star pH
Instrument (Thermo) measurement, for viscosity, using Brookfield visrometer RV DV- II+, with 24 DEG C, No. 6 mandrels
(Spindle), 30rpm condition measures.For character, takes appropriate amount (about 200mg) to be applied to skin, visually observe using 1 point
Character when clock.
The photo for shooting result macroscopic for its character is shown in Fig. 2 together with the pH of measurement and viscosity value.
According to fig. 2, pH be 5.0 situations below under, the viscosity of sample is low and trickles when in use, pH be 5.5 with
Under sample in the case where, principal component caused by being evaporated by solvent occurs when use and is precipitated.Under conditions of pH is 6.0 or more,
Principal component is not precipitated due to solvent evaporates when use, maintains transparent character.
Test example 2: property stability is tested when long-term preservation
For the sample of embodiment 1 and Comparative Examples 1 and 2, visually observed after being placed 1 month under the conditions of 25 DEG C, 60%RH,
Confirm character in actual use.It the results are shown in Fig. 3.
Test result, in the case of example 1, there is no principal component precipitatings after placing 1 month, even if using
When, also there is no variations for character, but in the case where comparative example 1 and 2, white precipitate occur when being used for a long time 1 month,
Confirm that the precipitating is made of principal component crystallizes.
Test example 3: the harsh conditions stability inferior test (impurity) being respectively formulated
Under the conditions of 60 DEG C, impurity stability test is implemented for the gel of embodiment 1,4,5 and comparative example 5,6,7.It closes
In test method(s) and analytic approach, with reference to British Pharmacopoeia (BP) " Ketoprofen Gel (ketoprofen gel) " impurity item, with HPLC points
Analyse (A) each impurity (Unknown impurities, unknown impuritie) and (B) total impurities.
It the results are shown in (A) and (B) of Fig. 4.
According to (A) and (B) of Fig. 4 as a result, the comparison that the comparative example 5 and pH that amount of alcohol is 40wt% or more are 7 or more
When the formula of example 6, significantly high impurity increment rate is shown compared with the gel of embodiment 1,4 or 5.In addition, relative to half
In the case that the amount of the total weight essential oil of solid pharmaceutical preparation is more than the comparative example 7 that 3.0 weight % are, for example, 3.5 weight %, compared to essence
The amount of oil is respectively the embodiment 1 of 0.5 weight % and the embodiment 5 that embodiment 4 or the amount of essential oil are 2.0 weight %, is shown aobvious
High impurity is write to increase.Specifically, in the comparative example 7 using the essential oil of 3.5 weight %, stability is carried out under severe conditions
When test, (A) each impurity and (B) total impurities increase by 0.2% or more when measuring after 1 week.
Test example 4: transdermal rate test
Using the gel of embodiment 1,3,5 and comparative example 3,4, the test of transdermal rate is carried out.
The test of transdermal rate is carried out using the pond Fu Langzi (Franz cell) and pigskin, is inhaled according in vitro skin
Acceptance test guide, design sample number (n=6) and sampling time point (6 time points).In Fu Langzi diffusion cell (Franz
Diffusion cell) used in receiver medium use pH 7.4 phosphate buffer (PBSbuffer), with temperature be 32
± 0.5 DEG C, 600rpm condition tested (with reference to International Journal of Pharmaceutical
The 3rd phase of volume 16 of Compounding (2012)), BP ketoprofen gel is utilized according to the condition of following Table 3 about sample analysis
(BP Ketoprofen gel) content test method(s) is tested.
[table 3]
It the results are shown in Fig. 5 and following table 4.
[table 4]
Test result, initial stage absorptivity is similar, but starts to show after 6 hours, the transdermal rate of embodiment 1,3 and 5
It is about the 140~250% of comparative example 3 and 4.The content of essential oil is the comparative example 3 of 0.5 weight % or more and the content of essential oil is
The comparative example 4 of 0.2 weight % is significantly high compared to transmitance.But comparative example 3 shows that transmitance is significant compared with embodiment 1 and 3
It is low.Specifically, comparative example 3 (for 0.5 weight %) identical as the essential oil content of embodiment 1 and ethanol content is identical (for 30.0 weights
Amount), but compared with Example 1, transdermal rate is significantly low, it is believed that this is because even if being used together with ethyl alcohol an adequate amount of
Essential oil, but in the case where being unsatisfactory for specific pH condition and range, the amount being absorbed by the skin because principal component is precipitated is reduced.Think,
In pH 6.0~6.5 and embodiment 1 and 3 containing 0.5% or more essential oil is not precipitated due to principal component, thus it is shown that more
High transdermal rate.It confirms, the case where embodiment 3 that the content of essential oil is 1.0% and reality that the content of essential oil is 0.5%
The case where applying example 1 is compared, transdermal rate somewhat higher.
Therefore, above-mentioned test result is shown, in the case where 6.0~6.5 condition of pH and essential oil content are 0.5% or more,
The transdermal rate of principal component significantly improves.
Above for being described with centered on preferred embodiment.In the technical field of the invention
Those of ordinary skill is appreciated that in the range of not departing from intrinsic propesties of the invention, the present invention can be in the form of deformation
Implement.Therefore, should from illustrative viewpoint rather than embodiment disclosed above from the viewpoint of restriction.Model of the invention
Enclosing is indicated to belong to all differences in the range being equal with it by above description content representation by claims
It should be interpreted to be both contained in the present invention.
Claims (12)
1. a kind of semisolid preparation comprising Ketoprofen and gelling agent, the semisolid preparation includes the conduct of 25~35 weight %
The ethyl alcohol of the solvent of Ketoprofen and by pH be 6.0~6.5 in a manner of include physiologically compatible alkanolamine.
2. semisolid preparation according to claim 1, wherein the gelling agent is carboxyl vinyl polymer, methyl fibre
Tie up element, xanthan gum, diphenhydramine, methylcellulose, hydroxypropyl methyl cellulose (HPMC) or their any combination.
3. semisolid preparation according to claim 1, wherein the alkanolamine be selected from by triethanolamine, diethanol amine and
The group that tromethamine is constituted.
4. semisolid preparation according to claim 1, wherein the alkanolamine is triethanolamine.
5. semisolid preparation according to claim 1 also includes the essential oil of 0.5~3.0 weight %.
6. semisolid preparation according to claim 1 also includes the essential oil of 0.5~2.0 weight %.
7. semisolid preparation according to claim 5, wherein the essential oil includes 50% or more terpenes or aromatic series
Close object.
8. semisolid preparation according to claim 5, wherein the essential oil be neroli oil, lavender oil, rosemary oil,
Eucalyptus oil or their any mixture.
9. semisolid preparation according to claim 1, wherein the semisolid preparation is gel or emulsifiable paste.
10. semisolid preparation according to claim 1, wherein the Ketoprofen is dexketoprofen.
11. semisolid preparation according to claim 1, wherein the semisolid preparation is for analgesia or anti-inflammatory.
12. a kind of preparation method of gel according to any one of claim 1 to 11, includes the following steps:
The aqueous dispersions of carboxyl vinyl polymer are mixed and homogenized with the ethanol solution containing Ketoprofen and essential oil；And
By be added in resulting mixture physiologically compatible alkanolamine carry out in and with pH is adjusted to 6.0~
6.5 and form gel.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20170096386 | 2017-07-28 | ||
| KR10-2017-0096386 | 2017-07-28 | ||
| KR10-2018-0085836 | 2018-07-24 | ||
| KR1020180085836A KR20190013535A (en) | 2017-07-28 | 2018-07-24 | Semisolid formulation containing ketoprofen and a process for the preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109303762A true CN109303762A (en) | 2019-02-05 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810842051.7A Pending CN109303762A (en) | 2017-07-28 | 2018-07-27 | Semisolid preparation and preparation method thereof containing Ketoprofen |
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| Country | Link |
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| CN (1) | CN109303762A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4393076A (en) * | 1980-05-14 | 1983-07-12 | Hisamitsu Pharmaceutical Co., Inc. | Anti-inflammatory and analgesic gel composition |
| CN1259048A (en) * | 1997-06-04 | 2000-07-05 | 美纳里尼实验室公司 | Semisolid pharmaceutical formulation containing dexketoprofen trometamol |
| EP1234573A1 (en) * | 2001-02-22 | 2002-08-28 | Menarini France S.A. | Anti-inflammatory pharmaceutical compositions and their manufacturing process |
| CN102068405A (en) * | 2010-12-16 | 2011-05-25 | 天津工业大学 | Ketoprofen gel and preparation method thereof |
| CN103705437A (en) * | 2012-10-08 | 2014-04-09 | 天津金耀集团有限公司 | Ketoprofen gel |
-
2018
- 2018-07-27 CN CN201810842051.7A patent/CN109303762A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4393076A (en) * | 1980-05-14 | 1983-07-12 | Hisamitsu Pharmaceutical Co., Inc. | Anti-inflammatory and analgesic gel composition |
| CN1259048A (en) * | 1997-06-04 | 2000-07-05 | 美纳里尼实验室公司 | Semisolid pharmaceutical formulation containing dexketoprofen trometamol |
| EP1234573A1 (en) * | 2001-02-22 | 2002-08-28 | Menarini France S.A. | Anti-inflammatory pharmaceutical compositions and their manufacturing process |
| CN102068405A (en) * | 2010-12-16 | 2011-05-25 | 天津工业大学 | Ketoprofen gel and preparation method thereof |
| CN103705437A (en) * | 2012-10-08 | 2014-04-09 | 天津金耀集团有限公司 | Ketoprofen gel |
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