CN102670577B - A kind of photosensitiser composition, its application method and purposes - Google Patents
A kind of photosensitiser composition, its application method and purposes Download PDFInfo
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- CN102670577B CN102670577B CN201210162537.9A CN201210162537A CN102670577B CN 102670577 B CN102670577 B CN 102670577B CN 201210162537 A CN201210162537 A CN 201210162537A CN 102670577 B CN102670577 B CN 102670577B
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Abstract
The invention discloses a kind of photosensitiser composition, its application method and purposes.The photosensitiser composition includes the active ingredient being made of 5 aminolevulinic acids or derivatives thereof, and hydroxypropyl methyl cellulose (HPMC).Wherein, the mass ratio of active ingredient and hydroxypropyl methyl cellulose is 2:1~5:1.Said composition formula is simple, it is mixed with water by a certain percentage can quickly form gelatinous swelling body.Since 5 ALA and HPMC will not react, therefore without incompatibility, and two kinds of key components can be placed in same container and preserved, reduce the cost of production, packaging and preservation.Diagnosis is used to prepare the invention also discloses said composition or treats the purposes of the medicine of mucosal sites disease.
Description
Technical field
The invention belongs to field of pharmacology；It is more particularly it relates to a kind of containing 5-ALA or derivatives thereof
Composition and its application method, further relate to said composition be used to prepare diagnosis or treat mucosal sites disease medicine use
On the way.
Background technology
Optical dynamic therapy (PDT) is a kind of new technological means of comparison, has been used to treat various diseases.At present on
The be used for optical dynamic therapy and the active ingredient of diagnosis in city are mainly 5-ALA (5-ALA) or its ester.
It has been reported that 5-ALA or derivatives thereof can be used in treatment including precancerous lesions of uterine cervix, cervical carcinoma etc.
Various pernicious or nonmalignant skin, conjunctiva, respiratory tract alimentary canal and vagina mucosa, endometrium, urothelium lesion and
Tumor disease.For example, the methyl esters of the 5-ALA by Photocure ASA (Oslo, Norway) exploitationsAnd 5-ALA
Own esterThe 5-ALA Levulan of DUSA Pharmaceuticals (Canada) exploitationsIts
InIt is a kind of emulsion, for treating basal cell tumor；It is solution, for being filled into bladder diagnosis
Carcinoma of urinary bladder；And LevulanIt is then a preparation being made of two chambers, it is another to contain 5-ALA in a chamber
As soon as contain aqueous solution, during use extruding destroy chamber interval and 5-ALA can be dissolved rapidly, for treating skin disease.
However, although above-mentioned common emulsion or solution product have good clinical efficacy, body difficult to treat
The lesion of some mucosal sites of body, such as the lesion of gastrovascular cavity, and female reproductive system (such as urethra, uterine neck and vagina) disease
Become.Because if with emulsion or solution to above-mentioned mucosal sites dispenser, medicine is short in lesion superficial residence time, and mucous membrane by
Meeting secreting mucus are stimulated, waters down or even washes away the medicine coated in lesions position, cause lesions position drug absorption inadequate, give
Treatment zone is come difficult.
Therefore, there is the product being administered using gel form in the market in recent years.Such as Publication No.
The Chinese patent of CN1435261A discloses a kind of mucoadhesive delivery system for light power diagnosis treatment, by thermocoagulation agent, promotees to ooze
The gel forming materials of agent and cellulose compound form, and are liquid under low-temperature condition, are transformed into gel during body temperature after administration
State.Gelling agent means that the glop or half of solution, suspension or emulsion type is made admittedly with that can form the auxiliary material of gel in medicine
Body preparation, is suitable for being used locally for skin and body cavity enters nasal cavity, vagina and rectum.Gel substrate has water-based and oiliness point,
Aqueous gel matrix is generally by water, glycerine or propane diols and cellulose derivative, carbomer and alginate, tragacanth, bright
Glue, starch etc. are formed.
United States Patent (USP) US20080069857 disclose one kind can rapidly-soluble hydrophilic in-situ gel preparation precursor, bag
Include two kinds of different polysaccharide materials, such as the derivative and cellulose compound of HA.However, both polysaccharide material palpuses
Independently preserve, mixed when in use, making it, Quick cross-linking forms gel in water.
Therefore, this area is necessary the gel delivery formulation of further exploitation 5-ALA, to overcome the prior art
In medicament there are the problem of.
The content of the invention
It is an object of the present invention to provide a kind of composition containing 5-ALA or derivatives thereof, said composition
Formula is simple, can rapidly be swollen in water, form gelatinous swelling body.
To achieve the above object, the present invention provides a kind of photosensitiser composition, and the composition includes：
By 5-ALA (5-ALA) or its pharmaceutically acceptable salt or ester, or the work that their derivative is formed
Property component；With
Hydroxypropyl methyl cellulose (HPMC)；
Wherein, the mass ratio of the active ingredient and hydroxypropyl methyl cellulose is 2:1~5:1.
In a preference, the active ingredient is the hydrochloride of 5-ALA.
In another preference, the model of the hydroxypropyl methyl cellulose is：HPMC K100 or HPMC K4M.
In another preference, the mass ratio of the active ingredient and hydroxypropyl methyl cellulose is 3:1~4:1.
In another preference, the photosensitiser composition is also comprising at least one of following component：Metal-chelating
Agent, penetrating agent, bacteriostatic agent, lubricant or binder.
In another preference, the metal-chelator is selected from：Ethylenediamine tetra-acetic acid (EDTA), 1,2-diaminocyclohexane tetraacetic acid
(CDTA), diethylenetriamine pentaacetic acid (DTPA), Cyclen-N- tetraacethyls (DOTA) or ethylene glycol；
The penetrating agent is selected from：Dialkyl group substitution sulfoxide, deoxycholic acid are received, oleic acid, dimethyl sulfoxide or azone；
The bacteriostatic agent is selected from：Parabens compound, cationic surfactant or parabens
Compound；
The lubricant is selected from：Polyethylene glycol (PEG)；
The binder is selected from：Povidone (PVP).
In another preference, the metal-chelator is the sodium salt natrium adetate of ethylenediamine tetra-acetic acid (EDTA)
(EDTA-2Na)；It is preferred that the mass ratio of the metal-chelator and the active ingredient is：0.0001:1-0.0009:1.
In another preference, the bacteriostatic agent is ethyl hydroxy benzoate；It is preferred that the bacteriostatic agent with it is described activity into
Point mass ratio be：0.002:1-0.004:1.
In another preference, the lubricant is polyethylene glycol；It is preferred that the lubricant with it is described activity into
Point mass ratio be：0.01:1-0.05:1.
In another preference, the adhesive is povidone；It is preferred that the adhesive and the active ingredient
Mass ratio be：0.02:1-0.2:1.
In another preference, the composition further includes solvent；It is preferred that the solvent is ethanol.
The photosensitiser composition of the present invention, it is formulated simply, since 5-ALA and HPMC will not react, therefore without compatibility
Taboo, and two kinds of key components can be placed in same container and preserved, reduce the cost of production, packaging and preservation.
After medicine and dispenser is made in the photosensitiser composition of the present invention, it is ensured that adhesion and medicine of the medicine in mucosal sites
The excellent permeability of thing, so that the effect of improving photodynamic therapy.Especially for Lesions of Female Genital Tract, with traditional hand
Art therapy is compared, and significantly reduces the pain of patient.
The second object of the present invention is to provide a kind of method of photosensitizer drug-delivery preparation, including：It is photosensitive described in providing
Agent composition, swelling thing is mixed to form by the photosensitiser composition and water, the active ingredient and water in the swelling thing
Mass ratio is 1:9~1:3.
In a preference, the drug-delivery preparation can be directly administered in the affected part of patient (such as mucosal sites).
In another preference, the drug-delivery preparation is gelling agent.
In another preference, the mass ratio of the active ingredient and water in the swelling thing is 1:4.
Photosensitizer drug-delivery preparation prepared by method using the present invention is in stable condition, and storage is convenient.
The third object of the present invention is used to prepare diagnosis or controls in the composition purposes in a kind of technical solution one is provided
Treat the medicine of mucosal sites disease.
In another preference, the mucosal sites disease includes disease and disease in the female sexual system below alimentary canal.
In another preference, the disease in the female sexual system is precancerous lesions of uterine cervix (CIN).
The fourth object of the present invention is to provide a kind of medicine box diagnosed or treat mucosal sites disease.The medicine box bag
Include：
The first container, wherein equipped with the active ingredient being made of 5-ALA or derivatives thereof；And
Second container, wherein equipped with hydroxypropyl methyl cellulose.
More preferably, it is also equipped with least one of following component in the second container：Metal-chelator, penetrating agent,
Bacteriostatic agent, lubricant or binder.
More preferably, the metal-chelator is selected from：Ethylenediamine tetra-acetic acid (EDTA), 1,2-diaminocyclohexane tetraacetic acid (CDTA), two
Second pentaacetic acid (DTPA), Cyclen-N- tetraacethyls (DOTA) or ethylene glycol；The penetrating agent
It is selected from：Dialkyl group substitution sulfoxide, deoxycholic acid are received, oleic acid, dimethyl sulfoxide or azone；The bacteriostatic agent is selected from：Para hydroxybenzene first
Acid esters compound, cationic surfactant or parabens compound；The lubricant is selected from：Polyethylene glycol
(PEG)；The binder is selected from：Povidone (PVP).
Brief description of the drawings
Diagram is placed in Fig. 1, the sampling of drug release in vitro experiment.
The unit area Percutaneous permeability of Fig. 2, test formulation (embodiment 3) and reference preparation (reference examples 2) each time point
Comparison.
Embodiment
The present inventor discloses one kind by 5-ALA (5-ALA) and hydroxypropyl methyl first by depth studying
The photosensitiser composition that cellulose (HPMC) compatibility is prepared into, said composition can be swollen rapidly in water, be formed gelatinous
Swelling body；And it is in stable condition, storage is convenient, no incompatibility.
The present inventor have rated the applicability of some high molecular polymers and 5-ALA compatibilities.Choosing to high molecular polymer
Selecting not only needs, according to its property, also to combine actually considering for working condition.The selection of high molecular polymer should meet
Following basic demand：(1) can meet the needs of preparation is to viscosity；(2) requirement of pharmaceutic adjuvant is met；(3) not with preparation
Other compositions react；(4) dissolution time is relatively fast, easily controllable production process；(5) hydration time is short, it is impossible to has precipitation
Produce.
With reference to requirements above, the present inventor tests povidone (PVP), polyvinyl alcohol (PVA), carbomer
(Carbomer), the high molecular polymer such as hydroxypropyl methyl cellulose (HPMC), guar gum and poloxamer (Poloxamer).
These types of high molecular material is studied respectively, compares it and is swollen dissolution time, dissolved viscosity and hydrochloric acid ammonia ketone valeric acid
The characteristic such as the speed of aquation and dissolved state after mixing.Result of study shows that it is heavy that Acritamer 940 has with hydrochloric acid ammonia ketone valeric acid
Form sediment and react；Polyvinyl alcohol dissolving is excessively slow；PVP K30 viscosity cannot meet the requirements (30% PVP K30 aqueous solution it is glutinous
Degree is about 60mPas)；When poloxamer188 redissolves, phase transition temperature improves；Guar gum dissolving is slightly slow, and the gel of formation sticks
Degree is higher；Hydroxypropyl methyl cellulose can meet fast hydration and form the requirement of gel.
Hydroxypropyl methyl cellulose, which is commonly used for preparing in the prior art, oral and topical uses preparation.In oral formulations
In, framework material of the hydroxypropyl methyl cellulose mainly as tablet binder, thin film coating material and sustained-release tablet.Hydroxypropyl
Methylcellulose can also be used as topical gels agent.
The two kinds of models of HPMC K100 and K4M referred in the present invention are mainly used for the framework material of sustained-release tablet.The present invention
People has found that two kinds of materials can be used as topical gels agent, moreover, compared with solution dosage, which does not delay hydrochloric acid ammonia ketone
The release of valeric acid.
One advantage of the composition of the present invention is to quickly form gelling agent after preparation meets water, this is because high hydrophilic
Hydrochloric acid ammonia ketone valeric acid greatly accelerates the swelling rate of hydroxypropyl methyl cellulose.
The dissolving of the high molecular polymers such as hydroxypropyl methyl cellulose in a solvent need to be first swollen, and be then redissolved, swelling
Generally require to be lot more time to reach balance to dissolving.Therefore, macromolecule polymer solution is prepared to generally require for a long time.
In order to shorten the time, accelerate to complete the preparation process of macromolecule polymer solution frequently with the methods of scattered, heating and stirring.It is right
In hydroxypropyl methyl cellulose, the common method for accelerating its swelling is high concentration ethanol dispersion method and hot water dispersion method.And this
In invention, pass through hydroxypropyl methyl cellulose and the mixing with ratio in proper way of hydrochloric acid ammonia ketone valeric acid, you can fast after chance water
Speed forms the gelling agent with certain viscosity.
Viscosity resists the physical quantity of shear deformation characteristic for characterization liquid, with dynamic viscosity, dynamic viscosity or intrinsic viscosity
Deng expression.《Chinese Pharmacopoeia》2010 editions two annex VI G " viscosimetry " have recorded three kinds of viscosimetries, wherein, first
Method measures dynamic viscosity or dynamic viscosity with Ping Shi viscosimeters, and the second method measures dynamic viscosity, the 3rd method with Rotary Viscosimeter
Intrinsic viscosity is measured with Ubbelohde viscometer.Wherein the second method is suitable for the viscosity measurement of non-newtonian fluid.It is respectively 1 square to make area
Centimetre at a distance of 1 centimetre of two layers of liquid, when making relative motion with the speed of centimeters per second, resistance caused by inside liquid particle
As dynamic viscosity, in units of Pas.
In order to reach superior technique effect, selectively, (but not limited to) can also be added in composition of the invention
Following components：Metal-chelator, penetrating agent, bacteriostatic agent, lubricant or binder.The metal-chelator can improve the present invention
The activity of photosensitizer in composition, so as to increase curative effect of medication.Its mechanism of action is：Iron ion is incorporated in ferrous a flat iron plate for making cakes and enzyme with Pp
Under the action of form ferroheme, so as to add the accumulation of PpIX, therefore be improved the activity of photosensitizer.The lubrication
The mobility for acting as material after raising is pelletized of agent.
Various conventional carriers or auxiliary material can also be added in the composition of the present invention, such as antioxidant, spices, pigment, are helped
Flow agent, pH buffer substance etc..These additives are all known to those skilled in the art.
The composition of the present invention can be made into being suitable for being mixed to form the various formulations of gelling agent, such as powder with water
(pulvis), granule.
Come from other preventions or treatment for mucosal sites disease in addition, can also contain in the composition of the present invention
The medicine of effect.
After raw material and its formula used is learnt, the photosensitiser composition of the present invention can easily be prepared.
Preparation method includes：The photosensitiser composition and water are mixed to form swelling thing, the active ingredient in the swelling thing with
The mass ratio of water is 1:9~1:3.The swelling thing can deliver medicine to the mucosal sites of patient directly as drug-delivery preparation.
Present invention also offers a kind of medicine box, it contains diagnosis or treats the medicine box of mucosal sites disease, including：The present invention
The photosensitiser composition；More preferably, it further comprises in the medicine box and instruct clinical patients to be said using the use of the medicine box
Bright book, wherein the water compatible method of photosensitiser composition, ratio etc. can be recorded.
With reference to specific embodiment, the present invention is further explained.It is to be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the invention.The experimental method of actual conditions is not specified in the following example, usually according to conventional strip
Part, or according to the condition proposed by manufacturer.Unless otherwise stated, otherwise percentage and number are calculated by weight；Liquid is dense
Degree is calculated by w/v.
(1) preparation of coagulant liquid
(1) aminoguanidine hydrochloride ketone valeric acid (5-ALA) is taken, and model is respectively the HPMC of K100 and K4M, it is stand-by.
(2) in technology preparation ratio (being shown in Table 1), 5-ALA and HPMC is mixed, is added to the water, be configured to embodiment 1-7 and
The coagulant liquid of reference examples 1.Wherein, 5-ALA concentration only refers to the 5-ALA concentration after excluding HPMC.
(2) swell test
The coagulant liquid of each embodiment and reference examples is recorded respectively, in process for preparation, when HPMC complete swellings are required
Between, and according to the viscosity measurement method (Chinese Pharmacopoeia of States Pharmacopoeia specifications》Second of 2010 editions two annex VIG " viscosimetry "
Determination method) each coagulant liquid of measure viscosity.Complete swelling refers to HPMC and forms homogeneous gel, no particle or solid content in water
In the presence of.
Test result is shown in Table 1.
Table 1
Test result shows that 5-ALA can greatly improve the swelling rate of HPMC with HPMC compatibilities.
In reference examples 1,5% pure HPMC lumps in dissolving, and standing 24 small fashion cannot be completely dissolved.And in embodiment
In the 5-ALA aqueous solutions of 1-7, HPMC that concentration is about 5~10% can complete swelling in 5 minutes, fully meet it is instant i.e.
Effect.
Wherein, when the ratio of 5-ALA and HPMC is 3:1~4:When 1 (i.e. embodiment 2,3), the coagulant liquid that is obtained it is viscous
Degree is optimal.
On the other hand, changing the concentration of 5-ALA influences less the swelling rate of HPMC.The medicinal concentration of 5-ALA is usual
For 20%, it is contemplated that the situation of some Special uses, in 5-ALA:HPMC==4:Under 1 proportioning, embodiment 5 and 6 measures respectively
5-ALA concentration is 10% and 30% situation, its swelling rate is equally respectively less than 5 minutes.
On the model of HPMC, by comparative example 3 and embodiment 7 as it can be seen that the swelling rate of the HPMC of different model
There is not too big difference.
(3) extracorporeal releasing test of medicine
Embodiment 3 and reference examples 2 are chosen, the non-sterilizing semi-solid medicament change research according to FDA issues in 1997 is instructed
Principle SUPAC-SS (Scale-up and Postapproval Changes:Chemistry,Manufacturing,and
Controls;In Vitro Release Testing and In Vivo Bioequivalence Documentation) in
Defined release in vitro research method is compared experiment.
Sample is set
Pellicle is sandwiched between Franz diffusion cells and acceptance pool.6.0~7.0ml PBS (pH are added in reception tank
7.0) it is used as reception liquid.Reception tank is placed in 37 DEG C of waters bath with thermostatic control, it is 200rpm to adjust magnetic agitation rotor speed.Reality is taken respectively
The swelling solution (being denoted as T) of example 3 and solution (being denoted as R) 0.5ml of reference examples 2 are applied, in supply pool, as shown in Figure 1 is spaced apart
Diffusion cell is in penetrating absorption instrument.
5 after administration, 0.2ml is sampled from reception tank within 10,20,40 and 80 minutes respectively, it is to be measured.At the same time supplement isothermal, etc. body
Long-pending blank reception liquid.T and R is distinguished 6 parts of parallel determination by assay method as described below.
Assay method
Reception liquid 0.1ml is quantitatively drawn, adding distilled water, be vortexed mixing, then draws solution 0.1ml, adds distillation to 1.0ml
Water is vortexed after mixing and draws 0.1ml to 1.0ml, adds distilled water to add borate buffer solution (pH value 8.2) 2.5ml to 2.0ml,
Fluorescamine acetone soln (0.2mg/ml) 0.5ml, is vortexed and mixes, determination sample fluorescence intensity.It is measured in the same method reagent blank fluorescence
Intensity, after fluorescent intensity subtracts reagent blank fluorescence intensity, substitutes into standard curve, calculates and accumulate transdermal amount.Measure Franz
Diffusion cell internal diameter, calculates transdermal area, obtains unit area and accumulates transdermal amount (Q).
Above-mentioned result of the test is referring to table 2.
The average value and SD of the unit area Percutaneous permeability at T and R each time points are calculated, as a result referring to table 3.
It is plotted against time with unit area Percutaneous permeability, each preparation accumulation transmission-time graph can be obtained, see Fig. 2.
The unit area of different time is accumulated into diffusing capacity to t1/2Mapping, obtained slope K and correlation coefficient r2, referring to
Table 4.
Table 2
Table 3
The in-vitro release rate of table 4, test formulation and reference preparation
| Numbering | Regression equation | Slope (K) | r2 |
| T1 | Q=18.403t1/2-2.588 | 18.403 | 0.970 |
| T2 | Q=17.817t1/2-1.717 | 17.817 | 0.998 |
| T3 | Q=19.315t1/2-2.019 | 19.315 | 0.980 |
| T4 | Q=21.874t1/2-3.315 | 21.874 | 0.969 |
| T5 | Q=26.458t1/2-4.425 | 26.458 | 0.996 |
| T6 | Q=25.515t1/2-4.882 | 25.515 | 0.987 |
| R1 | Q=17.745t1/2-0.019 | 17.745 | 0.989 |
| R2 | Q=19.298t1/2-1.266 | 19.298 | 0.998 |
| R3 | Q=22.739t1/2-2.839 | 22.739 | 0.986 |
| R4 | Q=26.214t1/2-3.326 | 26.214 | 0.962 |
| R5 | Q=27.784t1/2-4.386 | 27.784 | 0.997 |
| R6 | Q=23.779t1/2-1.978 | 23.779 | 0.968 |
As can be seen from Table 4, between 5min~80min, the unit area accumulation in 2 each hole of embodiment 3 and reference examples
Transit dose and the square root of time are linearly good, r2It is all higher than 0.96.
Statistics is found：The median of 36 ratio is 92.15%.By sorting from small to large, the 8th is 77.39%, the 29th
For 112.21%, i.e. 90% confidential interval of median is [77.39,112.21], within the scope of 75%-133%.According to SUPAC-
SS provides that test passes through.
Therefore, the swelling solution of embodiment 3 discharges in vitro compared with the solution for the reference examples 2 prepared according to the prior art
There is no significant difference in speed, drug effect can be guaranteed.
(4) preparation of pharmaceutical preparation
(1) hydrochloric acid ammonia ketone valeric acid (5-ALA) is taken, crushed 80 mesh sieves, it is stand-by.
(2) HPMC and natrium adetate are weighed (referring to table 5) in technology preparation ratio, stream is put together with hydrochloric acid ammonia ketone valeric acid
Change in bed, fluidisation mixing.
(3) PVP, PEG6000 and ethyl hydroxy benzoate are weighed in technology preparation ratio, adds absolute ethyl alcohol, stirring, until all
Dissolving.
(4) fluidized granulation is carried out, parameter setting is as follows：Inlet air temperature is set to：55~65 DEG C, the leaving air temp upper limit 1 is set to：
29 DEG C, the leaving air temp upper limit 2 is set to：40 DEG C, leaving air temp lower limit is set to：25 DEG C, concussion number is set to：4~10 times, during spraying
Between be set to：15~30 seconds.Selection granulation pattern carries out fluidisation mixing.Spraying system is carried out when temperature reaches the leaving air temp upper limit 1
Grain, atomisation pressure are adjusted in 0.25~0.30Mpa.Wriggling flow rate pump is adjusted to minimum.
(5) after pelletizing, it is 45~55 DEG C to adjust inlet air temperature, selects drying mode to be dried.After drying,
Inlet air temperature is set to 0 DEG C by adjusting parameter, is closed " air door " knob, is cooled down, and is less than 30 DEG C to temperature of charge.
(6) after whole grain, sampling carries out the inspection of semifinished product.
(7) after inspection of semifinished product qualification, dispensed, gland, labeling, be made 5-ALA and HPMC with such as
The part of embodiment 8-10 is dissipated with hydrochloric acid ammonia ketone valeric acid.
Table 5
In above-described embodiment, PVP is binder, PEG is lubricant, is granulation auxiliary element.
Metal-chelator and bacteriostatic agent play the role of synthesis and enhance product performance.Except the formula cited by embodiment 8-10
Outside, 1,2-diaminocyclohexane tetraacetic acid (CDTA), diethylenetriamine pentaacetic acid (DTPA), Isosorbide-5-Nitrae, 7,10- tetra- nitrogen also may be selected in metal-chelator
Triazacyclododecane-N- tetraacethyls (DOTA) and ethylene glycol.
Bacteriostatic agent may be selected from following a few major classes：Parabens, such as methyl hydroxybenzoate, ethyl hydroxy benzoate；Cation
Surfactant, such as cetyl ammonium, benzalkonium chloride, benzalkonium bromide；Alcohols, such as anesin；Organic mercury class, such as sulphur
Willow mercury, mercuric nitrate；Acids, such as sorbic acid；Parabens, such as：Methyl hydroxybenzoate, ethylparaben (ethyl hydroxy benzoate) etc..
Wherein, preferred parabens.
In addition can also add penetrating agent, as dialkyl group substitute sulfoxide, NaTDC, oleic acid, dimethyl sulfoxide (DMSO) and
Azone etc..The effect of wherein DMSO and azone is preferable, particularly preferred azone.
Embodiment 8, medicine box
A kind of medicine box is prepared, including：
The first container：The 5-ALA of 4 parts by weight is wherein housed, as active ingredient；
Second container：The HPMC K100 of 1 parts by weight are wherein housed；0.336 parts by weight povidone (PVP) K30；0.0128
Parts by weight ethyl hydroxy benzoate；The polyethylene glycol of 0.064 parts by weight；The natrium adetate of 0.002 parts by weight.
In use, it is first that the content in second container is soluble in water, the active ingredient in the first container is added, treats it
Affected part can be spread on after dissolving.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To be made various changes or modifications to the present invention, such equivalent forms equally fall within the model that the application the appended claims are limited
Enclose.
Claims (10)
1. a kind of photosensitiser composition, it is characterised in that the composition includes：
5-aminoketoglutarate hydrochloride as active component, and hydroxypropyl methyl cellulose；The active ingredient and hydroxypropyl
The mass ratio of methylcellulose is 2:1~5:1.
2. photosensitiser composition according to claim 1, it is characterised in that the active ingredient and hydroxypropyl methyl fiber
The mass ratio of element is 3:1~4:1.
3. photosensitiser composition according to claim 1, it is characterised in that also comprising at least one of following component：
Metal-chelator, penetrating agent, bacteriostatic agent, lubricant or binder.
4. photosensitiser composition according to claim 3, it is characterised in that
The metal-chelator is selected from：Ethylenediamine tetra-acetic acid, 1,2-diaminocyclohexane tetraacetic acid, diethylenetriamine pentaacetic acid, 1,4,7,10- tetra-
Azepine cyclododecane-N- tetraacethyls or ethylene glycol；
The penetrating agent is selected from：Dialkyl group substitution sulfoxide, deoxycholic acid are received, oleic acid, dimethyl sulfoxide or azone；
The bacteriostatic agent is selected from：Parabens compound, cationic surfactant or parabens compound；
The lubricant is selected from：Polyethylene glycol；
The binder is selected from：Povidone.
A kind of 5. method for preparing photosensitizer drug-delivery preparation, it is characterised in that including：
Any photosensitiser compositions of claim 1-4 are provided, the photosensitiser composition and water are mixed to form swelling
Thing, the mass ratio of the active ingredient and water in the swelling thing is 1:9~1:3.
6. any photosensitiser compositions of claim 1-4 are in the medicine for preparing diagnosis or treatment mucosal sites disease
Purposes.
7. purposes according to claim 6, it is characterised in that：The mucosal sites disease include alimentary canal below disease and
Disease in the female sexual system.
8. purposes according to claim 7, it is characterised in that：The disease in the female sexual system is precancerous lesions of uterine cervix.
9. a kind of medicine box diagnosed or treat mucosal sites disease, it is characterised in that the medicine box includes：
The first container, wherein equipped with 5-aminoketoglutarate hydrochloride as active component；And
Second container, wherein equipped with hydroxypropyl methyl cellulose；
Also, the mass ratio of the active ingredient and hydroxypropyl methyl cellulose is 2:1~5:1.
10. medicine box as claimed in claim 9, it is characterised in that be also equipped with the second container in following component extremely
Few one kind：Metal-chelator, penetrating agent, bacteriostatic agent, lubricant or binder.
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| ES2895851T3 (en) * | 2016-04-01 | 2022-02-22 | Trioptotec Gmbh | Photosensitizer dispersion and use thereof |
| CN105963698A (en) * | 2016-05-29 | 2016-09-28 | 金新 | Ointment for photochemical adjuvant therapy and preparation method and application thereof |
| CN108379580B (en) * | 2018-03-27 | 2021-03-12 | 四川大学 | 5-aminolevulinic acid gel composition and application thereof |
| CN108434100A (en) * | 2018-04-27 | 2018-08-24 | 中南大学湘雅三医院 | A kind of spraying photosensitiser composition for photodynamic therapy treatment nasopharynx cavum laryngis disease |
| CN114259561A (en) * | 2021-12-16 | 2022-04-01 | 上海复旦张江生物医药股份有限公司 | Photosensitizer and preparation method and application thereof |
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