CN100569292C - A kind of reversal temperature sensitive injection type implantable drug supporter material - Google Patents
A kind of reversal temperature sensitive injection type implantable drug supporter material Download PDFInfo
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- CN100569292C CN100569292C CNB2005100768835A CN200510076883A CN100569292C CN 100569292 C CN100569292 C CN 100569292C CN B2005100768835 A CNB2005100768835 A CN B2005100768835A CN 200510076883 A CN200510076883 A CN 200510076883A CN 100569292 C CN100569292 C CN 100569292C
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- cellulose derivative
- polysaccharide
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- polyethylene glycol
- gel
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- 239000000463 material Substances 0.000 title claims abstract description 48
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 229940079593 drug Drugs 0.000 title claims abstract description 25
- 238000002347 injection Methods 0.000 title claims abstract description 24
- 239000007924 injection Substances 0.000 title claims abstract description 24
- 229920002678 cellulose Polymers 0.000 claims abstract description 35
- 239000001913 cellulose Substances 0.000 claims abstract description 35
- 150000004676 glycans Chemical class 0.000 claims abstract description 35
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 35
- 239000005017 polysaccharide Substances 0.000 claims abstract description 35
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 16
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 238000005185 salting out Methods 0.000 claims abstract description 13
- 239000007943 implant Substances 0.000 claims abstract description 12
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- 239000012876 carrier material Substances 0.000 claims abstract description 4
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- 235000010980 cellulose Nutrition 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 229960003943 hypromellose Drugs 0.000 claims description 6
- 229920000609 methyl cellulose Polymers 0.000 claims description 6
- 239000001923 methylcellulose Substances 0.000 claims description 6
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 5
- 235000010413 sodium alginate Nutrition 0.000 claims description 5
- 239000000661 sodium alginate Substances 0.000 claims description 5
- 229940005550 sodium alginate Drugs 0.000 claims description 5
- 229920001661 Chitosan Polymers 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 235000010489 acacia gum Nutrition 0.000 claims description 4
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000230 xanthan gum Substances 0.000 claims description 4
- 235000010493 xanthan gum Nutrition 0.000 claims description 4
- 229920001285 xanthan gum Polymers 0.000 claims description 4
- 229940082509 xanthan gum Drugs 0.000 claims description 4
- 229920000896 Ethulose Polymers 0.000 claims description 3
- 239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 claims description 3
- 239000001509 sodium citrate Substances 0.000 claims description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 235000011008 sodium phosphates Nutrition 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 abstract description 8
- 238000001879 gelation Methods 0.000 abstract description 8
- 229920000573 polyethylene Polymers 0.000 abstract description 8
- 238000001647 drug administration Methods 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 230000008961 swelling Effects 0.000 abstract description 4
- 208000028389 Nerve injury Diseases 0.000 abstract description 3
- 230000002490 cerebral effect Effects 0.000 abstract description 3
- 238000002513 implantation Methods 0.000 abstract description 3
- 208000014674 injury Diseases 0.000 abstract description 3
- 229920002521 macromolecule Polymers 0.000 abstract description 3
- 230000008764 nerve damage Effects 0.000 abstract description 3
- 230000008733 trauma Effects 0.000 abstract description 3
- 210000001215 vagina Anatomy 0.000 abstract description 3
- 230000002209 hydrophobic effect Effects 0.000 abstract description 2
- 230000003993 interaction Effects 0.000 abstract description 2
- 239000012567 medical material Substances 0.000 abstract description 2
- 230000002441 reversible effect Effects 0.000 abstract description 2
- 230000001112 coagulating effect Effects 0.000 description 11
- 239000003937 drug carrier Substances 0.000 description 7
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 2
- 229960001381 glipizide Drugs 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920005601 base polymer Polymers 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
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Abstract
The invention discloses a kind of reverse temperature-sensitive type injection type implant carrier material that belongs to field of medical materials.Form by the by weight/volume of gel rubber material component by the salt of salting out by cellulose derivative, Polyethylene Glycol, polysaccharide with to cellulose derivative.The present invention is by adding the finite concentration polysaccharide in " cellulose derivative-Polyethylene Glycol-salt " system, strengthened the hydrophobic interaction between the system macromolecule, accelerated the gelation rate of system, improved gel strength, aquation and degree of swelling have been reduced, improved the stability of gel, release rate of drugs has slowed down.The sol solution of this material is injectable at room temperature, have excellent biological compatibility and biological degradability, avoid operation to implant and the taking-up preparation, can be used as the drug administration carrier of subdermal implantation, biological tissue's reparation skeleton, vagina, eye, cerebral trauma treatment, nerve injury treatment.
Description
Technical field
The invention belongs to field of medical materials, it is a kind of reversal temperature sensitive injection type implantable drug supporter material in definite saying.
Background technology
Embedded type drug delivery system (Implantable Drug Delivery Systems is hereinafter to be referred as IDDS) is that a class underwent operative implants or subcutaneous, or imports subcutaneous control release preparation through puncture, can play the long-term steadily purpose of administration.Development along with pharmaceutics and materialogy, depend on the change of external conditions such as temperature, pH, ionic strength, electric field, magnetic field and the intelligent macromolecule material that solubility property suddenlys change takes place, especially those injectables, good biocompatibility, in vivo can biodegradable material, owing to avoided operation in the overall process of administration, improved patient's compliance greatly, in IDDS, obtained using widely.
The dissolved state of temperature sensitive type material in water is subjected to externally temperature influence and transformation mutually between solution and the semisolid takes place.The material of low temperature liquid, high temperature semisolidization is referred to as " reversal temperature sensitive " material, and some this base polymer is that liquid state or solution are collosol state at normal temperatures, and the injection back forms gel or semisolidization down at body temperature (37 ℃), becomes original position semisolid Drug Storage.Compare with " forward is temperature sensitive " material of high-temperature liquid state, low temperature semisolidization, when drug administration by injection, " reversal temperature sensitive " material has overcome the shortcoming of high temperature injection, has avoided the body of burning, and therefore has been subjected to paying close attention to more widely.
The mixed solution of some cellulose derivative, Polyethylene Glycol and salt has good reversible reversal temperature sensitive characteristic, can at room temperature implant by injection, forms the release of physical gel Drug Storage.But swelling is easily taken place by solvation in cellulose derivative in the body environment, thereby increase the gel hole, aggravation is played salting out, is lowered into the loss of the salt of glue temperature, cause the part of this physical gel even all disintegrate, gel Drug Storage mechanical strength low and can't the drawbacks limit that exist steady in a long-term the range of application of this system.Therefore, " cellulose derivative-Polyethylene Glycol-salt " system can't realize the purpose of long-term controlled administration in the prior art.
Summary of the invention
The objective of the invention is to develop a kind of reversal temperature sensitive injection type implantable drug supporter material.
The objective of the invention is to be achieved by the following scheme: a kind of reversal temperature sensitive injection type implantable drug supporter material, this implant carrier material is fully dissolving in hot water with cellulose derivative and polysaccharide, be cooled to the solution that adds the Polyethylene Glycol aqueous solution after 4 ℃ and cellulose derivative is had the salt of salting out, regulate pH value to 7.4, under 4 ℃, stir and spend the night, obtain gel rubber material; It is characterized in that: the by weight/volume of each component is a cellulose derivative in the gained gel rubber material: Polyethylene Glycol: polysaccharide: salt=0.5～3 that cellulose derivative is had salting out: 4～12: 0～2.5: 2～6.
Described cellulose derivative comprises one or more mixtures of material in hydroxypropyl cellulose, hypromellose, ethylhydroxyethylcellulose and the methylcellulose.
Described polysaccharide comprises one or more mixtures of material in gelatin, arabic gum, chitosan, xanthan gum and the sodium alginate.
Described have the salt of salting out to comprise hydrochlorate, phosphate, sulfate, lactate or citrate to cellulose derivative.
The invention has the beneficial effects as follows: the present invention is a kind of reversal temperature sensitive injection type implantable drug supporter material, is colloidal sol under room temperature or low temperature state, implants patient part or subcutaneous by injection system, and original position takes place rapidly solidifies, as the Drug Storage release.By in existing " cellulose derivative-Polyethylene Glycol-salt " system, adding the finite concentration polysaccharide, strengthened the hydrophobic interaction between the system macromolecule, improve the gelation rate and the gel strength of system, reduced system aquation and degree of swelling, improved the stability of gel.Simultaneously, system has faster gelation rate, gel strength and homogeneity preferably near physiological pH, have better control slow release characteristic for medicine.Selected material all has excellent biological compatibility and biological degradability, harmless, avoid operation to implant and the taking-up preparation, can be used as the drug administration carrier of subdermal implantation, biological tissue's reparation skeleton, vagina, eye, cerebral trauma treatment, nerve injury treatment.Implant by injection system with the room temperature collosol state, and form the release of semi-solid gel Drug Storage in position.It has excellent mechanical intensity and stability in the body environment, degree of swelling is little, is that the ideal of long-term implant carrier is selected, and satisfies clinical demand widely.
Description of drawings
Fig. 1 polysaccharide concentration is to the influence curve of solidification kinetics.
Fig. 2 polysaccharide influences gel strength.
Fig. 3 polysaccharide is to the influence curve of coagulating property.
Fig. 4 polysaccharide is to the coagulating property influence curve.
Fig. 5 polysaccharide viscosity is to the figure that influences of gel rubber material modulus of shearing.
Fig. 6 is that polysaccharide is to 5-fluorouracil drug accumulation release rate influence curve.
Fig. 7 is that polysaccharide is to methotrexate drug accumulation release rate influence curve.
Fig. 8 is that polysaccharide is to methotrexate drug accumulation release rate influence curve.
The specific embodiment
The present invention is a kind of reversal temperature sensitive injection type implantable drug supporter material with excellent mechanical intensity and stability, this implant carrier material is fully dissolving in hot water with cellulose derivative and polysaccharide, be cooled to the solution that adds the Polyethylene Glycol aqueous solution after 4 ℃ and cellulose derivative is had the salt of salting out, regulate pH value to 7.4, under 4 ℃, stir and spend the night, obtain gel rubber material; The by weight/volume of each component is a cellulose derivative in the gained gel rubber material: Polyethylene Glycol: polysaccharide: salt=0.5～3 that cellulose derivative is had salting out: 4～12: 0～2.5: 2～6.
Above-mentioned cellulose derivative comprises one or more mixtures of material in hydroxypropyl cellulose, hypromellose, ethylhydroxyethylcellulose and the methylcellulose.
Above-mentioned polysaccharide comprises one or more mixtures of material in gelatin, arabic gum, chitosan, xanthan gum and the sodium alginate.
Above-mentioned have the salt of salting out to comprise hydrochlorate, phosphate, sulfate, lactate or citrate to cellulose derivative.
Above-mentioned cellulose derivative, polysaccharide and cellulose derivative is had the selection of the salt of salting out come out through a large amount of experiment screenings of inventor, their cooperate the reversal temperature sensitive injection type formula drug carrier material that obtains to have excellent mechanical intensity and stability.
For the adding that polysaccharide is described has improved mechanical strength and the stability that has " cellulose derivative-Polyethylene Glycol-salt " reversal temperature sensitive injection type implantable drug supporter material now, the medicine rate of release betwixt that slowed down now illustrates as follows:
Embodiment 1:
The prescription of gel rubber material is for the influence of system coagulating property:
1. polysaccharide adds the influence to " cellulose derivative-Polyethylene Glycol-salt " reversal temperature sensitive injection type formula drug carrier material coagulating property.
The by weight/volume of gel rubber material component is formed: methylcellulose is 1.5; Gelatin is respectively 0,1 and 1.5; Polyethylene Glycol is 8; Sodium chloride is 3.5.Regulate the pH to 7.4 of above-mentioned sol solution, be packed as 4 kinds of samples by polysaccharide content, every kind of sample carries out 3 groups of parallel laboratory tests.By digital display rotor viscometer detect the hydrosol 37 ℃ than viscosity under the low-shearing force over time, shear rate is 1rpm, draws system viscosity change curve in time, the external coagulating property of representation system, as shown in Figure 1.As seen, the new material that adds polysaccharide still has the reversal temperature sensitive characteristic, and along with the increase of polysaccharide concentration, the one-tenth glue speed of system is accelerated, and wherein the content of polysaccharide is added to after 1, can shorten to gelling time about 5 minutes.
2. cellulose derivative concentration is to the influence of reversal temperature sensitive injection type formula drug carrier material coagulating property.
The by weight/volume of gel rubber material component is formed: hypromellose is respectively 0.5,1,2,2.5; Arabic gum is 1; Polyethylene Glycol is 8; Sodium sulfate is 3.5.Experimental implementation is with 1 described among the embodiment 1, the coagulating property of system as shown in Figure 2, along with cellulose derivative concentration raises, the system gelation rate is accelerated.
3. Polyethylene Glycol concentration is to the influence of reversal temperature sensitive injection type formula drug carrier material coagulating property.
The by weight/volume of gel rubber material component is formed: hydroxypropyl cellulose is 2; Xanthan gum is 1; Polyethylene Glycol is respectively 0,2,4,8; Sodium phosphate is 3.5.Experimental implementation is with 1 described among the embodiment 1, the coagulating property of system as shown in Figure 3, along with Polyethylene Glycol concentration raises, the system gelation rate is accelerated.
4. cellulose derivative there is the concentration of salt of salting out to the influence of reversal temperature sensitive injection type formula drug carrier material coagulating property.
The by weight/volume of gel rubber material component is formed: the equal amount of mixture of methylcellulose/hypromellose is 2; Chitosan is 1; Polyethylene Glycol is 8; Sodium citrate is respectively 2,3,3.5,4,6.Experimental implementation is with 1 described among the embodiment 1, and the coagulating property of system increases the concentration of above-mentioned salt as shown in Figure 4 within the specific limits, can accelerate the system gelation rate.
The viscosity of polysaccharide is to the influence of " cellulose derivative-Polyethylene Glycol-salt " reversal temperature sensitive injection type formula drug carrier material gel strength.
The by weight/volume of gel rubber material component consists of hypromellose: 2; Sodium alginate (low sticking, in sticking, high sticking): 1; Polyethylene Glycol: 8; The equal amount of mixture of sodium dihydrogen phosphate and dibastic sodium phosphate: 3.5.
Gel strength characterizes with the shear modulus G of gel, at sectional area A
0And height L
0Cylindrical gel batten on apply certain pressure F, measure the height L that sample is compressed to after the 30s relaxation
1Strain-stress relation can be used equation F/A
0=-G (λ-λ
-2) characterize, wherein, λ=L
1/ L
0Be deformation ratio (λ=1.0～0.7), thus shear modulus G that can calculated for gel.
As shown in Figure 5, contrast does not contain the blank sample of polysaccharide, and the different viscosities polysaccharide that adds the content 1 of polysaccharide has all improved the intensity of gel rubber material largely.
Embodiment 3
Polysaccharide adds the influence to " cellulose derivative-Polyethylene Glycol-salt " reversal temperature sensitive injection type formula drug carrier material drug release feature.Selecting 5-fluorouracil, methotrexate, glipizide respectively for use is model drug.
The by weight/volume of gel rubber material component consists of methylcellulose: 2; Sodium alginate: 0～1; Polyethylene Glycol: 8; Sodium citrate: 3.5.Regulate pH to 7.4,3 groups of parallel laboratory tests are done in packing.
Release conditions: the water-bath shaker, dissolution medium: PBS buffer solution (pH=7.4,0.15M); Temperature: 37 ℃: rotating speed: 100rpm.Period sampling measuring discharges the content of liquid Chinese medicine, calculates the drug accumulation release rate.5-fluorouracil, methotrexate, glipizide drug loading are 2mg/mL, and release profiles is seen accompanying drawing 6,7,8 respectively.Contrast does not contain the system of polysaccharide, adds concentration and be 1% the polysaccharide rate of releasing drug of system to above-mentioned three kinds of medicines that slowed down.
In sum, the present invention has added polysaccharide in " cellulose derivative-Polyethylene Glycol-salt " system on the basis, the new reversal temperature sensitive injection type formula implanted gel material of formation, and gelation rate, gel strength, gel stability have all had raising.Simultaneously, system has faster gelation rate, gel strength and homogeneity preferably near physiological pH, all have better control slow release characteristic for several model drugs.The sol solution of material is injectable at room temperature, and have excellent biological compatibility and biological degradability, harmless, avoid operation to implant and take out preparation, therefore can be used as the drug administration carrier of subdermal implantation, biological tissue's reparation skeleton, vagina, eye, cerebral trauma treatment, nerve injury treatment.
Claims (1)
1. reversal temperature sensitive injection type implantable drug supporter material, this implant carrier material is fully dissolving in hot water with cellulose derivative and polysaccharide, be cooled to the solution that adds the Polyethylene Glycol aqueous solution after 4 ℃ and cellulose derivative is had the salt of salting out, regulate pH value to 7.4, under 4 ℃, stir and spend the night, obtain gel rubber material; It is characterized in that: the by weight/volume of each component is a cellulose derivative in the gained gel rubber material: Polyethylene Glycol: polysaccharide: salt=0.5～3 that cellulose derivative is had salting out: 4～12: 0～2.5: 2～6; Wherein polysaccharide is one or more the mixture in gelatin, arabic gum, chitosan, xanthan gum and the sodium alginate; Described cellulose derivative is one or more the mixture in hydroxypropyl cellulose, hypromellose, ethylhydroxyethylcellulose and the methylcellulose; It is described that cellulose derivative is had the salt of salting out is the equal amount of mixture of sodium chloride, sodium citrate or sodium dihydrogen phosphate and dibastic sodium phosphate.
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| CNB2005100768835A CN100569292C (en) | 2005-06-20 | 2005-06-20 | A kind of reversal temperature sensitive injection type implantable drug supporter material |
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|---|---|---|---|
| CNB2005100768835A CN100569292C (en) | 2005-06-20 | 2005-06-20 | A kind of reversal temperature sensitive injection type implantable drug supporter material |
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| CN1698902A CN1698902A (en) | 2005-11-23 |
| CN100569292C true CN100569292C (en) | 2009-12-16 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8536230B2 (en) | 2006-01-25 | 2013-09-17 | University Of Virginia Patent Foundation | Methods for regulating gelation of polysaccharide solutions and uses thereof |
| CN100591391C (en) * | 2006-07-28 | 2010-02-24 | 中国科学院上海微系统与信息技术研究所 | Implantation micro-electrode having integrated medicinal agent releasing function, its manufacturing method and application |
| CN101612437B (en) * | 2009-01-09 | 2011-09-14 | 清华大学 | In-situ implantation drug delivery system of naltrexone microsphere-hydrogel matrix |
| CN101953775B (en) * | 2010-09-17 | 2012-05-23 | 郑州大学 | Hydrogel nanoparticles used as injectable subcutaneous implant agent |
| CN104083320B (en) * | 2014-06-26 | 2017-01-11 | 复旦大学 | Injectable drug-loaded xanthan gum/methyl cellulose composite solution and preparation method thereof |
| CN108295318B (en) * | 2018-01-31 | 2021-07-06 | 西安泰科迈医药科技股份有限公司 | Temperature-sensitive injectable lacrimal passage suppository and preparation method thereof |
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