CN108309927A - A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride and preparation method thereof - Google Patents
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride and preparation method thereof Download PDFInfo
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Abstract
The present invention discloses a kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride and preparation method thereof, which is prepared by the raw material of following weight percent：Phosphatidase 1 5~40%, glyceride 60~70%, cosolvent 1~20%, doxorubicin hydrochloride 0.01~2%, photosensitizer 0.001~0.2%.The light-operated sustained release liquid crystal gel preparation viscosity of doxorubicin hydrochloride of the present invention is low, good fluidity, is easy to inject, in tumor or the injection of tumor week or postoperative tumor intracavitary place after can quickly form gel with liquid crystal structure, being capable of slow release doxorubicin hydrochloride in situ；Illumination causes gel with liquid crystal structure to undergo phase transition drug release rate increase, this preparation can not only extend drug treating time, reduce times for spraying, reduce the toxic side effect of drug, and it can be according to the cancer pathology situation of patient, illumination number or time are adjusted to adjust the release of drug, drug release on demand is realized, greatly enhances the bioavilability of drug.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular, to a kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride
And preparation method thereof.
Background technology
Lysotropic liquid crystal is mainly the orderly system that is formed by one or more Amphi-pathic compounds and solvent, inside have one
Each and every one lattice forms, and it is gel that the strong interaction force between ordered arrangement and amphiphile, amphiphilic molecule between lattice, which makes it in appearance,
Shape.Lysotropic liquid crystal is gradually available for the load of a variety of drugs since the characteristics of its own structure has attracted the concern of numerous scientists
Body can achieve the effect that the various polar medicines of long-acting slow-release in vivo.
Adriamycin is a kind of anthracene nucleus antineoplastic antibiotic, can inhibit the synthesis of RNA and DNA, to prevent tumour cell
Growth, antitumor spectra is wider, has an effect to kinds of tumors, belongs to cell cycle nonspecific agent (CCNSA), to the tumour of various growth cycles
Cell has killing effect.To various other cancers such as acute leukemia, malignant lymphoma, breast cancer, sarcoma, lung cancer, carcinoma of urinary bladder
Disease is all effective in cure.Clinical administration is mostly intravenous drip at present, but adriamycin cannot penetrate blood-brain barrier, and the medicine is rapid after intravenous
It is distributed whole body, has strong toxic side effect, is mainly manifested in：Cardiac toxic, less serious case show as arrhythmia cordis, and severe one carries out
Property Myocardial damage and congestive heart failure occurs；Cause leucocyte and decrease of platelet, bone marrow suppression；Trichomadesis；Alimentary canal
Reaction, nausea, anorexia；Drug overflows can cause tissue ulcer and necrosis outside blood vessel.These toxic side effects limit Ah mould
Extensive use of the element in clinical chemotherapy, although dosage is very big, the ratio that can reach lesions position performance curative effect is very low.
Chinese CN101234205A patent applications disclose a kind of " high molecule adriamycin bonding medicine with target function
Nano capsule ", the Nano capsule are formed by two kinds of polyethylene glycol-polylactic acid block copolymer Hybrid assemblings, one of which block
The polylactic acid chain of copolymer is terminated with adriamycin, and the molar ratio in Nano capsule is 98-70%；Another block copolymer
Polyglycol chain be terminated with lactose, the molar ratio in Nano capsule be 2-30%.In the patent application scheme, connection
Adriamycin on polylactic acid chain segment is in capsule core, by the duplicate protection of polylactic acid and polyethylene glycol, has slow-release function；
The lactose for being connected to the polyethylene glycol end of the chain is in outer capsule layer, has target function, Nano capsule is made to preferentially enter carrying lactose
The cell of receptor.But since not only molecular weight is larger but also is a kind of chain for the polyethylene glycol-polylactic acid block copolymer
Shape structure, therefore the segment of the overwhelming majority is, one winds the inside for being embedded in nano particle, and other end is emerging in nano particle
Surface.So, slow releasing function is just lost when adriamycin is emerging in the surface of nano particle, when lactose group is wound packet
Just do not have target function when being embedded in the inside of nano particle.Further, since being by a molecule-between the lactic acid molecules of polylactic acid
Made of-COOH the dehydrating condensations of OH and another molecule, and this ester bond is connected between adriamycin and polylactic acid
It is more fragile for amide key connection, chain rupture is susceptible to during biodegradation, on Doxorubicin molecules at this time often
The one section of polylactic acid that can in succession and influence drug effect.
It is to avoid chemotherapeutics in vivo to non-tumor group to the targeting of tumor tissue by changing administration route to improve drug
One of knit distribution, improve its curative effect, the method for safety.The country reported in the Chinese medicines such as silibinin, Osthole containing pair
Adriamycin cardiotoxicity has the active constituent of protective effect.But so far, still lack ideal drug can reduce Ah
Mycin toxicity, while maintaining or enhancing its curative effect, and accomplish according to the patient's condition, to discharge drug on demand.Therefore, it is badly in need of carrying
For a kind of doxorubicin hydrochloride gel with liquid crystal structure preparation with light-operated with slow releasing function.
Invention content
In response to the problems existing in the prior art, the purpose of the present invention is to provide a kind of bioavilability height, toxic side effect are small
And can light-operated release long-acting slow-release effect injectable gel with liquid crystal structure preparation.
It is a further object to provide the doxorubicin hydrochloride it is light-operated sustained release liquid crystal gel preparation preparation method,
This preparation method is simple, and production and cost of material are low, and is easy industrialization production.
In order to achieve the object, the technical solution adopted by the present invention is：
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Fat 15~40%, glyceride 50~70%, cosolvent 10~30%, doxorubicin hydrochloride 0.01~2%, photosensitizer 0.001~
0.2%；
The phosphatide includes phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylserine, phosphatidyl glycerol, phosphatidyl-4
At least one of alcohol, sphingomyelins；
The glyceride includes glyceryl dioleate, olein, tristerin, tripalmitin Pork and beans
At least one of cool olein, glyceryl laurate ester；
The cosolvent includes chloroform, dichloromethane, ethyl alcohol, methanol, middle long chain fatty acids, medium chain fatty acid, length
At least one of chain fatty acid, peanut oil, soybean oil, corn oil, castor oil, sesame oil；
The photosensitizer includes gold nanometer cage, gold nanorods, Jenner's grain of rice, ferroso-ferric oxide, graphene, carbon nano rod,
At least one of organic dyestuff substance.
Preferably, the light-operated sustained release liquid crystal gel preparation of the doxorubicin hydrochloride, by the raw material system of following weight percent
It is standby to form：It is phosphatidase 1 5~35%, glyceride 52~65%, cosolvent 12~28%, doxorubicin hydrochloride 0.05~1.5%, photosensitive
Agent 0.01%~0.1%.
Preferably, the doxorubicin hydrochloride lysotropic liquid crystal gel preparation, by the raw material preparation of following weight percent
At：Phosphatidase 2 5~35%, glyceride 52~60%, cosolvent 12~20%, doxorubicin hydrochloride 0.1~0.8%, photosensitizer
0.03%~0.08%.
Preferably, the phosphatide is phosphatidyl choline (SPC).
Preferably, the glyceride is glyceryl dioleate (GDO).
Preferably, the cosolvent is ethyl alcohol.
Preferably, the photosensitizer is organic dyestuff substance, and the organic dyestuff substance is IR780, IR820 (new indoles
Cyanines are green), it is indocyanine green, at least one of Prussian blue.
It is furthermore preferred that the photosensitizer is IR820.
Preferably, the present invention uses IR820 as photothermal conversion agent, phosphatide, glyceride and cosolvent are as hydrochloric acid
Adriamycin carrier.The IR820 has high photothermal conversion efficiency, and does not have apparent toxic side effect to human body, can be by
Organism metabolism is excreted through urine.The phosphatide, glyceride, have no toxic and side effect to human body, and tissue compatible is good, and can be by people
Body is metabolized, and the reconstruction of such as cell membrane in entire life process, cell signalling are participated in.The present invention injects targeting moiety
Afterwards, water can be met and form gel with liquid crystal structure, form drug " reservoir ", relatively for free drug, the present invention significantly slows drug diffusion
Speed, extend dosage period, reduce administration number of times, to greatly improve the compliance of patient；In addition, the present invention can pass through
Patient's medicine-feeding part near infrared light illumination is given, converts light energy into thermal energy using photosensitizer, and then change the phase of gel with liquid crystal structure,
Finally realize that Drug controlled release rate to meet the needs of different pathological process is to drug dose, greatly improves complying with for patient
Property.
What doxorubicin hydrochloride lysotropic liquid crystal gel preparation of the present invention was selected is all natural material, non-immunogenicity,
Good biocompatibility, and doxorubicin hydrochloride liquid crystal precursors encounter the gel that body fluid is formed and can be metabolized completely in vivo, and
Its metabolite can participate in internal vital movement as nutriment, will not cause the inflammatory reaction of body.
The present invention also provides the preparation methods of the light-operated sustained release liquid crystal gel preparation of the doxorubicin hydrochloride, including following step
Suddenly：After phosphatide, glyceride, doxorubicin hydrochloride and photosensitizer are mixed, it is completely dissolved under the action of cosolvent to get to described
The light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride.
Compared with prior art, the beneficial effects of the invention are as follows：
(1) the light-operated sustained release liquid crystal gel preparation viscosity of doxorubicin hydrochloride of the present invention is low, good fluidity, is easy to inject, and
Gel with liquid crystal structure can be quickly formed after injection, it being capable of slow release doxorubicin hydrochloride in situ；Drug treating time is extended, is reduced
Times for spraying, improves drug bioavailability；The excessively high caused toxic side effect of drug concentration is avoided simultaneously.
(2) when the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride of the present invention can be by the illumination of regulating near-infrared light
Between, illumination number reaches on-demand controlled release drug, improves the effective rate of utilization of drug.
(3) what the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride of the present invention was selected is all natural material, and nothing is exempted from
The gel that epidemic focus, good biocompatibility, and doxorubicin hydrochloride liquid crystal precursors encounter body fluid formation can complete generation in vivo
It thanks, and its metabolite can participate in internal vital movement as nutriment, will not cause the inflammatory reaction of body.
(4) preparation method of the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride of the present invention is simple, and raw material is easy to get to production
Technique low energy consumption, equipment cost and cost of material are relatively low, are easy to industrialization.
Description of the drawings
It is formed after the light-operated sustained release liquid crystal gel preparation phase transformation of doxorubicin hydrochloride that Fig. 1 is prepared by embodiment 1-3 solidifying
The petrographic microscope figure of glue；
Before and after the light-operated sustained release liquid crystal gel preparation near infrared light illumination of doxorubicin hydrochloride that Fig. 2 is prepared for embodiment 2
The picture of formed gel；
Fig. 3 is that the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride that embodiment 1-3 is prepared is not added under illumination condition
Doxorubicin hydrochloride cumulative release figure；
Fig. 4 is hydrochloric acid under the conditions of the light-operated sustained release liquid crystal gel preparations of doxorubicin hydrochloride that are prepared of embodiment 1-3 are light-operated
Adriamycin cumulative release figure.
Specific implementation mode
The light-operated sustained release liquid crystal gel preparation precursor of doxorubicin hydrochloride prepared by the present invention carries out doxorubicin hydrochloride release and investigates.
Experimental method：The light-operated sustained release liquid crystal gel preparation of suitable doxorubicin hydrochloride is weighed in the glass tube of clean dried, is then added
After 7.4 phosphate buffers of pH of certain volume, sealing is put into constant-temperature table and carries out oscillation release, constant-temperature table parameter is set
It sets：37 DEG C of temperature, rotating speed 100rpm.Every two days to an illumination, illumination condition is：Light application time is 2min, and irradiation power is close
Degree is 0.5w/cm2, is sampled respectively at different time points, the dissolution medium of same volume is then added into delivery systme.It takes out
Dissolution medium place -20 DEG C it is spare, through multi-function microplate reader detect dissolution medium in doxorubicin hydrochloride contents.
The light-operated sustained release liquid crystal gel preparation precursor of doxorubicin hydrochloride of the present invention can be used for injection, the note used daily
The amount of penetrating is every time 1~2ml, and service life is 4-6 weeks primary, and preferably 5 weeks primary.Doxorubicin hydrochloride prepared by the present invention is light-operated
It is sustained liquid crystal one week accumulative release rate of gel preparation and is less than 25%, there is good slow release effect, medication can be greatly prolonged
Period reduces times for spraying.
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.Unless stated otherwise, the present invention uses reagent, method and apparatus is the art conventional reagent, methods
And equipment.
Embodiment 1
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 25.99%, glyceryl dioleate 60%, absolute ethyl alcohol 13.88%, doxorubicin hydrochloride 0.1%, IR8200.03%.
The preparation method of the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride is as follows：By the weight percent by phosphorus
After phosphatidylcholine, glyceryl dioleate, doxorubicin hydrochloride, IR820 are mixed, the nothing of the weight percent is then added
Water-ethanol is uniformly mixed on mixer, is allowed to be completely dissolved to get to the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, close
Envelope, 4 DEG C of preservations.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
2.35 ± 0.13% are each about with illumination preparation is added, as a result as shown in Figure 3 and Figure 4, it may be possible to whether due to illumination not
Its liquid crystal phase is influenced, into without influencing its cumulative release rate.
Embodiment 2
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 35%, glyceryl dioleate 52%, absolute ethyl alcohol 12.12%, doxorubicin hydrochloride 0.8%, IR8200.08%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
With add illumination preparation to be respectively 10.05 ± 0.43%, 22.25 ± 0.21%, as a result as shown in Figure 3 and Figure 4, illustrate salt
The sour light-operated sustained release liquid crystal gel preparation of adriamycin can be good at the release of regulating medicine to light sensitive.
Embodiment 3
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 25%, glyceryl dioleate 54.45%, absolute ethyl alcohol 20%, doxorubicin hydrochloride 0.5%, IR8200.05%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
21.15 ± 0.18% are each about with illumination preparation is added, as a result as shown in Figure 3 and Figure 4, it may be possible to whether due to illumination not
Its liquid crystal phase is influenced, into without influencing its cumulative release rate.
Embodiment 4
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 15%, glyceryl dioleate 56.94%, absolute ethyl alcohol 28%, doxorubicin hydrochloride 0.05%, IR820 0.01%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
19.15 ± 0.18% are each about with illumination preparation is added, to illumination-insensitive.
Embodiment 5
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 34.4%, glyceryl dioleate 52%, absolute ethyl alcohol 12%, doxorubicin hydrochloride 1.5%, IR820 0.1%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
17.65 ± 0.23% are each about with illumination preparation is added, to illumination-insensitive.
Embodiment 6
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 20%, glyceryl dioleate 65%, absolute ethyl alcohol 13.95%, doxorubicin hydrochloride 1%, IR820 0.05%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
20.35 ± 0.18% are each about with illumination preparation is added, to illumination-insensitive.
Embodiment 7
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 15%, glyceryl dioleate 70%, absolute ethyl alcohol 14.989%, doxorubicin hydrochloride 0.01%, IR820
0.001%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
9.15 ± 0.15% are each about with illumination preparation is added, to illumination-insensitive.
Embodiment 8
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 37.8%, glyceryl dioleate 50%, absolute ethyl alcohol 10%, doxorubicin hydrochloride 2%, IR820 0.2%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
21.85 ± 0.25% are each about with illumination preparation is added, to illumination-insensitive.
Embodiment 9
A kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, is prepared by the raw material of following weight percent：Phosphorus
Phosphatidylcholine 39.65%, glyceryl dioleate 50%, absolute ethyl alcohol 10%, doxorubicin hydrochloride 0.3%, IR820 0.05%.
Preparation method is same as Example 1.
The appearance that product is made in the present embodiment is shallow yellow transparent solution, illustrates that each materials compatibility is good, is uniformly mixed.-4
DEG C storage 6 months and centrifugal treating after without lamination, illustrate that product shelf stability is good.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of the present embodiment doxorubicin hydrochloride
23.05 ± 0.30% are each about with illumination preparation is added, to illumination-insensitive.
Comparative example 1
The present embodiment provides a kind of light-operated sustained release liquid crystal gel preparation precursors of doxorubicin hydrochloride, by following weight percent
Raw material is prepared：Phosphatidyl choline 42%, glyceryl dioleate 45%, absolute ethyl alcohol 12%, doxorubicin hydrochloride 0.8%,
IR8200.2%.
The preparation method of the light-operated sustained release liquid crystal gel preparation precursor of doxorubicin hydrochloride doxorubicin hydrochloride of this comparative example and inspection
Survey method is the same as embodiment 2.
The appearance that product is made in this comparative example is the solution of muddiness, and each materials compatibility is poor, unmixed uniform.Storage 3
There is lamination after a month or centrifugal treating, illustrates that product stability is poor.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of this comparative example doxorubicin hydrochloride
With add illumination preparation more than 40%, and to illumination-insensitive.
Comparative example 2
The present embodiment provides a kind of light-operated sustained release liquid crystal gel preparation precursors of doxorubicin hydrochloride, by following weight percent
Raw material is prepared：Phosphatidyl choline 35%, glyceryl monooleate 52%, absolute ethyl alcohol 12%, doxorubicin hydrochloride 0.8%,
IR8200.2%.
The preparation method of the light-operated sustained release liquid crystal gel preparation precursor of doxorubicin hydrochloride doxorubicin hydrochloride of this comparative example and inspection
Survey method is the same as embodiment 2.
The appearance that product is made in this comparative example is the solution of muddiness, and each materials compatibility is poor, unmixed uniform.Storage 2
There is lamination after a month or centrifugal treating, illustrates that product stability is poor.
Doxorubicin hydrochloride is not added with illumination in one week in the light-operated sustained release liquid crystal gel preparation precursor of this comparative example doxorubicin hydrochloride
With add illumination preparation more than 55%, and to illumination-insensitive.
Application examples 1
The light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride prepared by embodiment 1-3 is weighed in right amount in bottle, is then added
Enter excessive phosphate buffer (pH 7.4), after standing overnight, remove extra phosphate buffer, then takes suitable solidifying
Glue is in polarized light microscopy microscopic observation and takes pictures.The results are shown in Figure 1, is from left to right followed successively by the doxorubicin hydrochloride of embodiment 1-3
Light-operated sustained release liquid crystal gel preparation forms the petrographic microscope figure for corresponding to gel after meeting water.Different SPC/GDO ratios hydrochloric acid Ah
Mycin it is light-operated sustained release liquid crystal gel preparation meet water after formed corresponding gel liquid crystalline phase difference, by figure it is found that embodiment 1
Without polarization texture, it is consistent with cubic phase；Embodiment 2 has apparent polarization texture with embodiment 3, has anisotropy, is in
Maltese cross shape has typical layered liquid crystal texture, shows that liquid crystalline phase is trans- six side phase.
Application examples 2
The light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride of the preparation of embodiment 2 is weighed in right amount in bottle, is then added
Excessive phosphate buffer (pH 7.4), after standing overnight, is allowed to complete gelation, laser hot spot is then navigated to liquid
On brilliant gel, illumination, light application time 2min are carried out, light radiation density is 0.5w/cm2.The results are shown in Figure 2, from a left side to
The right side be followed successively by embodiment 2 the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride meet after the illumination for forming corresponding gel after water and
Aspect graph before illumination.After near infrared light shines, gel with liquid crystal structure is undergone phase transition, and the mobility of liquid crystal increases, mechanical performance drop
It is low, uniformity enhancing, no lamination.
The above, only of the invention illustrates embodiment, not to the present invention in any form with substantial limitation,
It should be pointed out that for those skilled in the art, under the premise of not departing from the method for the present invention, that makes several changes
Protection scope of the present invention is also should be regarded as into supplement.All those skilled in the art, do not depart from spirit of that invention and
In the case of range, using the equivalent variations of a little change, modification and differentiation that disclosed above technology contents are made, it is
The equivalent embodiment of the present invention；Meanwhile any equivalent variations that all substantial technologicals according to the present invention do the embodiment
Change, modification and differentiation, still fall within protection scope of the present invention.
Claims (9)
1. a kind of light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride, which is characterized in that by the raw material system of following weight percent
It is standby to form：Phosphatidase 1 5~40%, glyceride 50~70%, cosolvent 10~30%, doxorubicin hydrochloride 0.01~2%, photosensitizer
0.001~0.2%；
The phosphatide includes phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylserine, phosphatidyl glycerol, phosphatidylinositols, sheath
At least one of phosphatide；
The glyceride includes glyceryl dioleate, olein, tristerin, tripalmitin mace oil
At least one of acid glyceride, glyceryl laurate ester；
The cosolvent includes chloroform, dichloromethane, ethyl alcohol, methanol, middle long chain fatty acids, medium chain fatty acid, long-chain fat
At least one of fat acid, peanut oil, soybean oil, corn oil, castor oil, sesame oil；
The photosensitizer includes gold nanometer cage, gold nanorods, Jenner's grain of rice, ferroso-ferric oxide, graphene, carbon nano rod, organic
At least one of dye substance.
2. the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride according to claim 1, which is characterized in that by following weight
The raw material of percentage is prepared：Phosphatidase 1 5~35%, glyceride 52~65%, cosolvent 12~28%, doxorubicin hydrochloride
0.05~1.5%, photosensitizer 0.01%~0.1%.
3. the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride according to claim 1, which is characterized in that by following weight
The raw material of percentage is prepared：Phosphatidase 2 5~35%, glyceride 52~60%, cosolvent 12~20%, doxorubicin hydrochloride 0.1
~0.8%, photosensitizer 0.03%~0.08%.
4. according to the light-operated sustained release liquid crystal gel preparation of claims 1 to 3 any one of them doxorubicin hydrochloride, which is characterized in that
The phosphatide is phosphatidyl choline.
5. according to the light-operated sustained release liquid crystal gel preparation of claims 1 to 3 any one of them doxorubicin hydrochloride, which is characterized in that
The glyceride is glyceryl dioleate.
6. according to the light-operated sustained release liquid crystal gel preparation of claims 1 to 3 any one of them doxorubicin hydrochloride, which is characterized in that
The cosolvent is ethyl alcohol.
7. according to the light-operated sustained release liquid crystal gel preparation of claims 1 to 3 any one of them doxorubicin hydrochloride, which is characterized in that
The photosensitizer be organic dyestuff substance, the organic dyestuff substance be IR780, IR820, indocyanine green, it is Prussian blue in extremely
Few one kind.
8. the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride according to claim 7, which is characterized in that the photosensitizer
For IR820.
9. the preparation method of the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride described in claim 1, which is characterized in that including
Following steps：By phosphatide, glyceride, doxorubicin hydrochloride and photosensitizer mix after, be completely dissolved under the action of cosolvent to get
To the light-operated sustained release liquid crystal gel preparation of doxorubicin hydrochloride.
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| CN113081954A (en) * | 2021-05-25 | 2021-07-09 | 南昌大学第二附属医院 | Gel drug-loaded patch drug delivery system |
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