CN102670577A - Photo-sensitizer composition, and using method and application thereof - Google Patents
Photo-sensitizer composition, and using method and application thereof Download PDFInfo
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- CN102670577A CN102670577A CN2012101625379A CN201210162537A CN102670577A CN 102670577 A CN102670577 A CN 102670577A CN 2012101625379 A CN2012101625379 A CN 2012101625379A CN 201210162537 A CN201210162537 A CN 201210162537A CN 102670577 A CN102670577 A CN 102670577A
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Abstract
The invention discloses a photo-sensitizer composition, and a using method and application thereof. The photo-sensitizer composition contains an active ingredient consisting of 5-aminolevulinic acid (5-ALA) or derivative thereof and hydroxypropyl methyl cellulose (HPMC), wherein, the mass ratio of the active ingredient to HPMC is 2:1-5:1. The composition is simple in formula, and a gelatinous swelling body can be quickly formed by mixing the composition and water in a certain ratio. Because the 5-ALA does not react with HPMC, incompatibility is not produced; and two main components can be stored in the same container, so that the production, packing and storage costs are reduced. The invention also discloses application of the composition in preparation of medicaments for diagnosing or treating mucosal part diseases.
Description
Technical field
The invention belongs to field of pharmacology; More specifically, the present invention relates to a kind of compoistion and method of use of the 5-of containing aminolevulinic acid or derivatives thereof, also relate to the purposes that said composition is used to prepare diagnosis or treats the medicine of mucosal sites disease.
Background technology
Optical dynamic therapy (PDT) is a kind of newer technological means, has been used to treat various diseases.The active ingredient that is used for optical dynamic therapy and diagnosis that has gone on the market at present mainly is 5-aminolevulinic acid (5-ALA) or its ester.
Existing bibliographical information, the 5-ALA or derivatives thereof can be used in various pernicious or nonmalignant skin, conjunctiva, respiratory tract digestive tract and vaginal mucosa, endometrium, urothelium pathological changes and the ND that treatment comprises precancerous lesions of uterine cervix, cervical cancer etc.For example; By Photocure ASA (Oslo; The 5-ALA Levulan
of the methyl ester
of the 5-ALA that Norway) develops and own ester
the DUSA Pharmaceuticals (Canada) of 5-ALA exploitation wherein
is a kind of Emulsion, is used to treat basal cell tumor;
is solution, is used to be filled into the bladder diagnosing bladder cancer; Levulan
then is a preparation that is made up of two chambers; Another contains aqueous solution to contain 5-ALA in the chamber; Squeeze and destroy chamber interventricular septum just can be dissolved 5-ALA rapidly during use, is used to treat dermatosis.
Yet, though above-mentioned common Emulsion or solution product have the good clinical curative effect, be difficult to treat the pathological changes of some mucosal sites of health, such as the pathological changes of gastrovascular cavity, and female reproductive system (like urethra, cervix uteri and vagina) pathological changes.Because, if with Emulsion or solution to above-mentioned mucosal sites dispenser, medicine is short in the focus surface time of staying; And mucosa irriate meeting secreting mucus; Water down even wash away the medicine that is coated in lesions position, cause the lesions position drug absorption not enough, bring difficulty to treatment.
Therefore, on the market product that adopts gel form to carry out administration has appearred in recent years.Such as; Publication number is that the Chinese patent of CN1435261A discloses a kind of mucoadhesive delivery system that is used for the light power diagnosis treatment; One-tenth glue material by thermocoagulation agent, penetrating agent and cellulose compound is formed, and under low temperature state, is liquid, is transformed into gel state after the administration during body temperature.Gel means that medicine and the adjuvant that can form gel process the glop or the semi-solid preparation of solution, suspendible or emulsion type, is suitable for that the part is used for skin and body cavity is gone into nasal cavity, vagina and rectum.Gel substrate has the branch of aqueous and oiliness, and aqueous gel substrate generally is made up of water, glycerol or propylene glycol and cellulose derivative, carbomer and alginate, tragakanta, gelatin, starch etc.
U.S. Pat 20080069857 disclose a kind of can rapidly-soluble hydrophilic in-situ gel preparation precursor, comprise two kinds of different polysaccharide materials, for example the derivant of HA and cellulose compound.Yet these two kinds of polysaccharide materials must independently respectively be preserved, and mix in use, make it in water, be cross-linked to form gel fast.
Therefore, this area is necessary further to develop the gel delivery dosage form of 5-aminolevulinic acid, to overcome the problem that medicament of the prior art exists.
Summary of the invention
One of the object of the invention is to provide a kind of compositions of the 5-of containing aminolevulinic acid or derivatives thereof, and the said composition prescription is simple, and the rapid swelling of ability forms gelatinous swelling body in water.
For realizing above-mentioned purpose, the present invention provides a kind of photosensitiser composition, and said compositions comprises:
By 5-aminolevulinic acid (5-ALA) or its pharmaceutically acceptable salt or ester, or the active component of their derivant formation; With
Hydroxypropyl emthylcellulose (HPMC);
Wherein, the mass ratio of said active component and hydroxypropyl emthylcellulose is 2:1～5:1.
In a preference, said active ingredient is the hydrochlorate of 5-aminolevulinic acid.
In another preference, the model of described hydroxypropyl emthylcellulose is: HPMC K100 or HPMC K4M.
In another preference, the mass ratio of said active component and hydroxypropyl emthylcellulose is 3:1～4:1.
In another preference, described photosensitiser composition also comprises at least a in the following component: metal-chelator, penetrating agent, antibacterial, lubricant or adhesive.
In another preference, said metal-chelator is selected from: ethylenediaminetetraacetic acid (EDTA), 1,2-diaminocyclohexane tetraacetic acid (CDTA), diethylenetriamine pentaacetic acid (DTPA), 1,4,7,10-tetraazacyclododecanand-N-tetraacethyl (DOTA) or ethylene glycol;
Said penetrating agent is selected from: dialkyl group replaces that sulfoxide, deoxycholic acid are received, oleic acid, dimethyl sulfoxine or azone;
Said antibacterial is selected from: parabens chemical compound, cationic surfactant or Nipagin ester compounds;
Described lubricant is selected from: Polyethylene Glycol (PEG);
Described adhesive is selected from: polyvidone (PVP).
In another preference, described metal-chelator is the sodium salt disodium edetate (EDTA-2Na) of ethylenediaminetetraacetic acid (EDTA); Preferably, the mass ratio of described metal-chelator and said active component is: 0.0001:1-0.0009:1.
In another preference, described antibacterial is an ethyl hydroxybenzoate; Preferably, the mass ratio of described antibacterial and said active component is: 0.002:1-0.004:1.
In another preference, described lubricant is a Polyethylene Glycol; Preferably, the mass ratio of described lubricant and said active component is: 0.01:1-0.05:1.
In another preference, described binding agent is a polyvidone; Preferably, the mass ratio of described binding agent and said active component is: 0.02:1-0.2:1.
In another preference, described compositions also comprises solvent; Preferably, described solvent is an ethanol.
Photosensitiser composition of the present invention, its prescription is simple, because 5-ALA can not react with HPMC, thus no incompatibility, and can these two kinds of key components be placed the interior preservation of same container, reduced the cost of production, packing and preservation.
After photosensitiser composition of the present invention is processed medicine and dispenser, can guarantee medicine, thereby improve the curative effect of PDT in the tack of mucosal sites and the excellent permeability of medicine.Particularly, compare, alleviated patient's misery greatly with the conventional surgical therapy to the female reproductive system pathological changes.
Two of the object of the invention is to provide a kind of method of photosensitizer drug-delivery preparation; Comprise: described photosensitiser composition is provided; Said photosensitiser composition is mixed formation swelling thing with water, the said active component in this swelling thing and the mass ratio of water are 1:9～1:3.
In a preference, described drug-delivery preparation can directly deliver medicine to patient's affected part (like mucosal sites).
In another preference, described drug-delivery preparation is a gel.
In another preference, the said active component in the said swelling thing and the mass ratio of water are 1:4.
Adopt the photosensitizer drug-delivery preparation of method preparation of the present invention in stable condition, convenient for storing.
Three of the object of the invention is the compositions purposes in a kind of technical scheme one is provided, and is used to prepare the medicine of diagnosis or treatment mucosal sites disease.
In another preference, said mucosal sites disease comprises digestive tract below disease and disease in the female sexual system.
In another preference, said disease in the female sexual system is precancerous lesions of uterine cervix (CIN).
Four of the object of the invention is to provide the medicine box of a kind of diagnosis or treatment mucosal sites disease.Said medicine box comprises:
First container wherein is equipped with the active component that is made up of 5-aminolevulinic acid or derivatives thereof; And
Second container wherein is equipped with hydroxypropyl emthylcellulose.
More preferably, at least a in the following component also is housed in described second container: metal-chelator, penetrating agent, antibacterial, lubricant or adhesive.
More preferably, said metal-chelator is selected from: ethylenediaminetetraacetic acid (EDTA), 1,2-diaminocyclohexane tetraacetic acid (CDTA), diethylenetriamine pentaacetic acid (DTPA), 1,4,7,10-tetraazacyclododecanand-N-tetraacethyl (DOTA) or ethylene glycol; Said penetrating agent is selected from: dialkyl group replaces that sulfoxide, deoxycholic acid are received, oleic acid, dimethyl sulfoxine or azone; Said antibacterial is selected from: parabens chemical compound, cationic surfactant or Nipagin ester compounds; Described lubricant is selected from: Polyethylene Glycol (PEG); Described adhesive is selected from: polyvidone (PVP).
Description of drawings
Diagram is placed in the sampling of Fig. 1, medicine extracorporeal releasing test.
The comparison of the unit are accumulation transit dose of Fig. 2, preparation to be measured (embodiment 3) and each time point of reference preparation (reference examples 2).
The specific embodiment
The inventor discloses a kind of photosensitiser composition that is prepared into by 5-aminolevulinic acid (5-ALA) and hydroxypropyl emthylcellulose (HPMC) compatibility first through research in depth, said composition can be in water can rapid swelling, form gelatinous swelling body; And in stable condition, convenient for storing, no incompatibility.
The inventor has estimated the suitability of some high molecular polymers and 5-ALA compatibility.Selection to high molecular polymer not only need also will combine the actual of working condition to take all factors into consideration according to its character.The selection of high molecular polymer should be satisfied following basic demand: the demand of preparation to viscosity can be satisfied in (1); (2) meet the requirement of pharmaceutic adjuvant; (3) not with preparation in other compositions react; (4) dissolution time is fast relatively, is easy to control production process; (5) hydration time is short, can not have deposition to produce.
In conjunction with above requirement, the inventor has tested polyvidone (PVP), polyvinyl alcohol (PVA), carbomer (Carbomer), hydroxypropyl emthylcellulose (HPMC), guar gum and poloxamer high molecular polymers such as (Poloxamer).These several kinds of macromolecular materials are studied respectively, relatively characteristics such as the viscosity after its swelling dissolution time, the dissolving, the speed that mixes back aquation with hydrochloric acid ammonia ketone valeric acid and dissolved state.Result of study shows that Acritamer 940 and hydrochloric acid ammonia ketone valeric acid have precipitation; The polyvinyl alcohol dissolving is too slow; 30 POVIDONE K 30 BP/USP 30 viscositys can not meet the demands (viscosity of 30% 30 POVIDONE K 30 BP/USP, 30 aqueous solutions is about 60mPas); When poloxamer 407 redissolved, phase transition temperature improved; The guar gum dissolving is slightly slow, and the gel viscosity of formation is higher; Hydroxypropyl emthylcellulose can satisfy fast hydration and form the requirement of gel.
Hydroxypropyl emthylcellulose often is used to prepare oral and topical preparation in the prior art.In oral formulations, hydroxypropyl emthylcellulose is mainly as the framework material of tablet binder, thin film coating material and slow releasing tablet.Hydroxypropyl emthylcellulose also can be used as the topical gels agent.
Two kinds of models of HPMC K100 that mentions among the present invention and K4M are mainly used in the framework material of slow releasing tablet.The inventor finds that these two kinds of materials can be used as the topical gels agent, and, to compare with solution dosage, this gel does not delay the release of hydrochloric acid ammonia ketone valeric acid.
An advantage of compositions of the present invention is can form gel very soon after preparation is met water, and this is because high hydrophilic hydrochloric acid ammonia ketone valeric acid has been accelerated the swelling rate of hydroxypropyl emthylcellulose greatly.
The dissolving of high molecular polymers such as hydroxypropyl emthylcellulose in solvent needs first swelling, and then dissolving, and swelling to dissolving often needs just can reach balance for a long time.Therefore, the preparation macromolecule polymer solution generally needs for a long time.For the shortening time, often adopt methods such as dispersion, heating and stirring to quicken to accomplish the preparation process of macromolecule polymer solution.For hydroxypropyl emthylcellulose, its swollen method of quickening commonly used is high concentration ethanol dispersion method and hot water dispersion method.And among the present invention, in the mixing of suitable mode and ratio, form gel fast after can meeting water with certain viscosity through hydroxypropyl emthylcellulose and hydrochloric acid ammonia ketone valeric acid.
Viscosity is for characterizing the physical quantity of liquid opposing detrusion characteristic, with expressions such as dynamic viscosity, dynamic viscosity or intrinsic viscosities." 2010 editions two appendix VI G of Chinese pharmacopoeia " viscosimetry " have recorded three kinds of viscosimetries; Wherein, First method is measured dynamic viscosity or dynamic viscosity with the Ping Shi viscosimeter, and second method is measured dynamic viscosity with Rotary Viscosimeter, and the three therapeutic methods of traditional Chinese medicine is measured intrinsic viscosity with Ubbelohde viscometer.Wherein second method is applicable to the viscosity measurement of non-Newtonian fluid.Making area respectively is 1 square centimeter of two-layer liquid of 1 centimetre apart, and when doing operation relatively with the speed of centimeters per second, the inner resistance that is produced of liquid particle is dynamic viscosity, is unit with Pas.
In order to reach better technique effect, selectively, can also add (but being not limited to) following component in the compositions of the present invention: metal-chelator, penetrating agent, antibacterial, lubricant or adhesive.Described metal-chelator can improve the activity of photosensitizer in the present composition, thereby increases curative effect of medication.Its mechanism of action is: the effect that iron ion and Pp are combined in ferrous a flat iron plate for making cakes and enzyme forms haemachrome down, thereby has increased the accumulation of PpIX, therefore the activity of photosensitizer is improved.The flowability that act as raising granulation back material of described lubricant.
Can also add various conventional carriers or adjuvant in the compositions of the present invention, like antioxidant, spice, pigment, fluidizer, pH buffer substance etc.These additives all are that those skilled in the art know.
Compositions of the present invention can be made into to be suitable for to mix with water the various dosage forms that form gel, for example powder (powder), granule.
In addition, can also contain in the compositions of the present invention and come from other for the prevention of mucosal sites disease or the medicine of therapeutical effect.
After learning used raw material and prescription thereof, can prepare photosensitiser composition of the present invention easily.Method for preparing comprises: said photosensitiser composition is mixed forming the swelling thing with water, the said active component in this swelling thing and the mass ratio of water are 1:9～1:3.This swelling thing can directly deliver medicine to patient's mucosal sites as drug-delivery preparation.
The present invention also provides a kind of medicine box, and it contains the medicine box of diagnosis or treatment mucosal sites disease, comprising: photosensitiser composition of the present invention; More preferably, also comprise the operation instructions that direct clinical patient uses this medicine box in the described medicine box, wherein can put down in writing the water compatible method of photosensitiser composition, ratio etc.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise percentage ratio and umber calculate by weight; Strength of fluid is pressed w/v and is calculated.
(1) preparation of coagulant liquid
(1) get aminoguanidine hydrochloride ketone valeric acid (5-ALA), and model is respectively the HPMC of K100 and K4M, for use.
(2) in technology preparation ratio (seeing table 1), 5-ALA and HPMC are mixed, add in the entry, be mixed with the coagulant liquid of embodiment 1-7 and reference examples 1.Wherein, 5-ALA concentration only refers to exclude the 5-ALA concentration behind the HPMC.
(2) swell test
Write down the coagulant liquid of each embodiment and reference examples respectively; In process for preparation; The needed time of HPMC complete swelling, and measure the viscosity of each coagulant liquid according to the viscosity measurement method (second kind of algoscopy of 2010 editions two appendix VIG of Chinese pharmacopoeia " viscosimetry ") of pharmacopeia regulation.Complete swelling refers to that HPMC has formed the gel of homogeneous in water, and no granule or solid content exist.
Test result is seen table 1.
Table 1
Test result shows that 5-ALA and HPMC compatibility can improve the swelling rate of HPMC greatly.
In the reference examples 1,5% pure HPMC is caking when dissolving, and leaving standstill 24 little fashion can not dissolve fully.And in the 5-ALA of embodiment 1-7 aqueous solution, concentration be about 5～10% HPMC all can be in 5 minutes complete swelling, reached the effect of instant i.e. usefulness fully.
Wherein, when the ratio of 5-ALA and HPMC was 3:1～4:1 (being embodiment 2,3), the viscosity of the coagulant liquid that is obtained was best.
On the other hand, the concentration of change 5-ALA is little to the swelling rate influence of HPMC.The medicinal concentration of 5-ALA is generally 20%, considers the situation of some special use, and under the proportioning of 5-ALA:HPMC==4:1, it is 10% and 30% situation that embodiment 5 and 6 has measured 5-ALA concentration respectively, and its swelling rate is equally all less than 5 minutes.
About the model of HPMC, visible with embodiment 7 through comparative example 3, the swelling rate of the HPMC of different model does not have too big-difference.
(3) extracorporeal releasing test of medicine
Choose embodiment 3 and reference examples 2, according to non-sterilization semi-solid medicament change research guideline SUPAC-SS (Scale-up and Postapproval Changes:Chemistry, Manufacturing, the and Controls of FDA issue in 1997; In Vitro Release Testing and In Vivo Bioequivalence Documentation) the release in vitro research method of regulation compares test in.
Sample is provided with
Semipermeable membrane is sandwiched in the Franz diffusion cell and accepts between the pond.In reception tank, add 6.0～7.0ml PBS (pH 7.0) as receiving liquid.Reception tank is placed 37 ℃ of waters bath with thermostatic control, and regulating the magnetic agitation rotor speed is 200rpm.Get the swelling solution (note is made T) of embodiment 3 and solution (note the is made R) 0.5ml of reference examples 2 respectively, in supply pool, diffusion cell is placed in the transdermal tester in interval as shown in Figure 1.
After the administration 5,10,20,40 and 80 minutes respectively from reception tank sampling 0.2ml, to be measured.Replenish isothermal, isopyknic blank liquid that receives simultaneously.Press the described assay method of hereinafter T and R are distinguished 6 parts of parallel assays.
Assay method
Quantitatively draw and receive liquid 0.1ml, adding distil water is to 1.0ml, the vortex mixing; Draw this solution 0.1ml again, adding distil water is drawn 0.1ml to 1.0ml behind the vortex mixing; Adding distil water adds borate buffer solution (pH value 8.2) 2.5ml, fluorescamine acetone soln (0.2mg/ml) 0.5ml to 2.0ml; The vortex mixing, the working sample fluorescence intensity.Measure the reagent blank fluorescence intensity with method, after fluorescent intensity deducts the reagent blank fluorescence intensity, substitution standard curve, calculating cumulative transdermal amount.Measure Franz diffusion cell internal diameter, calculate the transdermal area, obtain unit are accumulation transdermal amount (Q).
Above-mentioned result of the test is referring to table 2.
Calculate the meansigma methods and the SD of the unit are accumulation transit dose of T and each time point of R, the result is referring to table 3.
With unit are accumulation transit dose the time is mapped, can obtain each preparation accumulation and see through-time graph, see Fig. 2.
The unit are of different time is accumulated diffusing capacity to t
1/2Mapping, slope K that obtains and correlation coefficient r
2, referring to table 4.
Table 2
Table 3
The in-vitro release rate of table 4, preparation to be measured and reference preparation
| Numbering | Regression equation | Slope (K) | r 2 |
| T 1 | Q=18.403t 1/2-2.588 | 18.403 | 0.970 |
| T 2 | Q=17.817t 1/2-1.717 | 17.817 | 0.998 |
| T 3 | Q=19.315t 1/2-2.019 | 19.315 | 0.980 |
| T 4 | Q=21.874t 1/2-3.315 | 21.874 | 0.969 |
| T 5 | Q=26.458t 1/2-4.425 | 26.458 | 0.996 |
| T 6 | Q=25.515t 1/2-4.882 | 25.515 | 0.987 |
| R 1 | Q=17.745t 1/2-0.019 | 17.745 | 0.989 |
| R 2 | Q=19.298t 1/2-1.266 | 19.298 | 0.998 |
| R 3 | Q=22.739t 1/2-2.839 | 22.739 | 0.986 |
| R 4 | Q=26.214t 1/2-3.326 | 26.214 | 0.962 |
| R 5 | Q=27.784t 1/2-4.386 | 27.784 | 0.997 |
| R 6 | Q=23.779t 1/2-1.978 | 23.779 | 0.968 |
Can find out that from table 4 between 5min～80min, the unit are accumulation transit dose and the square root of time in embodiment 3 and reference examples 2 each hole are linear good, r
2All greater than 0.96.
Statistics is found: the median of 36 ratios is 92.15%.By ordering from small to large, the 8th is 77.39%, the 29 is 112.21%, and promptly median 90% confidence interval is [77.39,112.21], all within the scope of 75%-133%.According to the SUPAC-SS regulation, test is passed through.
Therefore, the swelling solution of embodiment 3 is compared with the solution of the reference examples of preparing according to prior art 2, on in-vitro release rate, does not have significant difference, and drug effect can be guaranteed.
(4) preparation of pharmaceutical preparation
(1) get hydrochloric acid ammonia ketone valeric acid (5-ALA), pulverized 80 mesh sieves, for use.
(2) take by weighing HPMC and disodium edetate in technology preparation ratio (referring to table 5), put in the fluid bed with hydrochloric acid ammonia ketone valeric acid, fluidisation is mixed.
(3) take by weighing PVP, PEG6000 and ethyl hydroxybenzoate in the technology preparation ratio, add dehydrated alcohol, stir, until whole dissolvings.
(4) carry out fluidized granulation, parameter is provided with as follows: EAT is made as: 55～65 ℃, the leaving air temp upper limit 1 is made as: 29 ℃; The leaving air temp upper limit 2 is made as: 40 ℃; The leaving air temp lower limit is made as: 25 ℃, the concussion number of times is made as: 4～10 times, spray time is made as: 15～30 seconds.Selecting the granulation pattern to carry out fluidisation mixes.Equitemperature carries out spray granulation when arriving the leaving air temp upper limit 1, and atomisation pressure is adjusted at 0.25～0.30Mpa.The peristaltic pump flow rate regulation is to minimum.
(5) after granulation finished, regulating EAT was 45～55 ℃, selected drying mode to carry out drying.Behind dry the end, ordering parameter is made as 0 ℃ with EAT, closes " air door " knob, cools off, and is lower than 30 ℃ to temperature of charge.
(6) behind the granulate, the inspection of semifinished product is carried out in sampling.
(7) inspection of semifinished product qualified after, carry out steps such as packing, gland, labeling, loose with hydrochloric acid ammonia ketone valeric acid in the part that makes proportioning such as the embodiment 8-10 of 5-ALA and HPMC.
Table 5
In the foregoing description, PVP is that adhesive, PEG are lubricant, is the granulation auxiliary element.
Metal-chelator and antibacterial play the effect of comprehensively enhancing product performance.Except that the cited prescription of embodiment 8-10, metal-chelator also can be selected 1,2-diaminocyclohexane tetraacetic acid (CDTA), diethylenetriamine pentaacetic acid (DTPA), 1,4,7,10-tetraazacyclododecanand-N-tetraacethyl (DOTA) and ethylene glycol.
Antibacterial can be selected from following several big type: parabens, like methyl hydroxybenzoate, ethyl hydroxybenzoate etc.; Cationic surfactant is like bromination hexadecane ammonium, benzalkonium chloride, benzalkonium bromide etc.; Alcohols is like chlorobutanol; The organic mercury class is like thimerosal, Mercury pernitrate.; Acids is like sorbic acid; Parabens, for example: methyl hydroxybenzoate, ethyl hydroxybenzoate (ethyl hydroxybenzoate) etc.Wherein, preferred parabens.
Also penetrating agent be can add in addition, sulfoxide, NaTDC, oleic acid, dimethyl sulfoxine (DMSO) and azone etc. replaced like dialkyl group.Wherein the effect of DMSO and azone is better, preferred especially azone.
Embodiment 8, medicine box
Prepare a kind of medicine box, comprising:
First container: the 5-ALA of 4 weight portions wherein is housed, as active component;
Second container: the HPMC K100 that 1 weight portion wherein is housed; 0.336 weight portion polyvidone (PVP) K30; 0.0128 weight portion ethyl hydroxybenzoate; 0.064 the Polyethylene Glycol of weight portion; 0.002 the disodium edetate of weight portion.
During use, earlier that the content in second container is soluble in water, add the active component in first container again, treat can spread on the affected part after its dissolving.
All documents in that the present invention mentions are all quoted as a reference in this application, are just quoted such as a reference separately as each piece document.Should be understood that in addition after having read above-mentioned teachings of the present invention, those skilled in the art can do various changes or modification to the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. a photosensitiser composition is characterized in that, said compositions comprises:
By 5-aminolevulinic acid or its pharmaceutically acceptable salt or ester, or the active component of their derivant formation; With
Hydroxypropyl emthylcellulose;
Wherein, the mass ratio of said active component and hydroxypropyl emthylcellulose is 2:1～5:1.
2. photosensitiser composition according to claim 1 is characterized in that, said active ingredient is the hydrochlorate of 5-aminolevulinic acid.
3. photosensitiser composition according to claim 1 and 2 is characterized in that, the mass ratio of said active component and hydroxypropyl emthylcellulose is 3:1～4:1.
4. photosensitiser composition according to claim 1 and 2 is characterized in that, also comprises at least a in the following component: metal-chelator, penetrating agent, antibacterial, lubricant or adhesive.
5. photosensitiser composition according to claim 4 is characterized in that,
Said metal-chelator is selected from: ethylenediaminetetraacetic acid, 1,2-diaminocyclohexane tetraacetic acid, diethylenetriamine pentaacetic acid, 1,4,7,10-tetraazacyclododecanand-N-tetraacethyl or ethylene glycol;
Said penetrating agent is selected from: dialkyl group replaces that sulfoxide, deoxycholic acid are received, oleic acid, dimethyl sulfoxine or azone;
Said antibacterial is selected from: parabens chemical compound, cationic surfactant or Nipagin ester compounds;
Described lubricant is selected from: Polyethylene Glycol;
Described adhesive is selected from: polyvidone.
6. a method for preparing the photosensitizer drug-delivery preparation is characterized in that, comprising:
Claim 1-5 is provided arbitrary described photosensitiser composition, said photosensitiser composition is mixed forming the swelling thing with water, the said active component in this swelling thing and the mass ratio of water are 1:9～1:3.
7. the purposes of the arbitrary described photosensitiser composition of claim 1-5 in the medicine of preparation diagnosis or treatment mucosal sites disease.
8. purposes according to claim 7 is characterized in that: said mucosal sites disease comprises digestive tract below disease and disease in the female sexual system.
9. purposes according to claim 8 is characterized in that: said disease in the female sexual system is a precancerous lesions of uterine cervix.
10. the medicine box of diagnosis or treatment mucosal sites disease is characterized in that said medicine box comprises:
First container wherein is equipped with the active component that is made up of 5-aminolevulinic acid or derivatives thereof; And
Second container wherein is equipped with hydroxypropyl emthylcellulose; More preferably, at least a in the following component also is housed in described second container: metal-chelator, penetrating agent, antibacterial, lubricant or adhesive.
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| CN105708788A (en) * | 2016-02-24 | 2016-06-29 | 济南梵康医疗科技有限公司 | Method for preparing hydrochloric aminolevulinic acid nano emulsifiable paste |
| CN105963698A (en) * | 2016-05-29 | 2016-09-28 | 金新 | Ointment for photochemical adjuvant therapy and preparation method and application thereof |
| CN108379580A (en) * | 2018-03-27 | 2018-08-10 | 四川大学 | A kind of 5-ALA gel combination and its application |
| 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 |
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| CN105963698A (en) * | 2016-05-29 | 2016-09-28 | 金新 | Ointment for photochemical adjuvant therapy and preparation method and application thereof |
| CN108379580A (en) * | 2018-03-27 | 2018-08-10 | 四川大学 | A kind of 5-ALA gel combination and its application |
| 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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