CN117357480A - Composition for needleless percutaneous injection - Google Patents
Composition for needleless percutaneous injection Download PDFInfo
- Publication number
- CN117357480A CN117357480A CN202311681459.8A CN202311681459A CN117357480A CN 117357480 A CN117357480 A CN 117357480A CN 202311681459 A CN202311681459 A CN 202311681459A CN 117357480 A CN117357480 A CN 117357480A
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- CN
- China
- Prior art keywords
- phospholipid
- scar
- composition
- needle
- injection
- Prior art date
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- 239000007924 injection Substances 0.000 title claims abstract description 42
- 238000002347 injection Methods 0.000 title claims abstract description 42
- 239000000203 mixture Substances 0.000 title claims abstract description 40
- 231100000241 scar Toxicity 0.000 claims abstract description 63
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 44
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 44
- 208000002260 Keloid Diseases 0.000 claims abstract description 28
- 206010023330 Keloid scar Diseases 0.000 claims abstract description 28
- 210000001117 keloid Anatomy 0.000 claims abstract description 28
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 24
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 24
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 22
- 230000007935 neutral effect Effects 0.000 claims abstract description 22
- -1 phospholipid diselenide Chemical class 0.000 claims abstract description 18
- 230000008685 targeting Effects 0.000 claims abstract description 18
- 239000003112 inhibitor Substances 0.000 claims abstract description 11
- 210000002950 fibroblast Anatomy 0.000 claims description 40
- 230000001969 hypertrophic effect Effects 0.000 claims description 24
- 239000012528 membrane Substances 0.000 claims description 20
- 229960002117 triamcinolone acetonide Drugs 0.000 claims description 9
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 claims description 9
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 claims description 8
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 claims description 8
- 229960002537 betamethasone Drugs 0.000 claims description 8
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims description 8
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 claims description 8
- LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 6
- 229940083466 soybean lecithin Drugs 0.000 claims description 6
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 abstract description 26
- 210000000170 cell membrane Anatomy 0.000 abstract description 24
- 239000002502 liposome Substances 0.000 abstract description 14
- 239000000835 fiber Substances 0.000 abstract description 10
- 238000002156 mixing Methods 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 4
- 239000008280 blood Substances 0.000 abstract description 4
- 238000013268 sustained release Methods 0.000 abstract description 3
- 239000012730 sustained-release form Substances 0.000 abstract description 3
- 230000004044 response Effects 0.000 abstract description 2
- 206010020718 hyperplasia Diseases 0.000 abstract 1
- 230000002390 hyperplastic effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 14
- 238000005538 encapsulation Methods 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 12
- 238000009472 formulation Methods 0.000 description 11
- 238000011835 investigation Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 206010018910 Haemolysis Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 230000008588 hemolysis Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 229940117972 triolein Drugs 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 210000003022 colostrum Anatomy 0.000 description 4
- 235000021277 colostrum Nutrition 0.000 description 4
- 230000037311 normal skin Effects 0.000 description 4
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- 241000283977 Oryctolagus Species 0.000 description 2
- 240000007711 Peperomia pellucida Species 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000004815 dispersion polymer Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 2
- 208000032544 Cicatrix Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000007925 in vitro drug release testing Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Botany (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present embodiments provide compositions for needleless transdermal injection, including scar inhibitors, specific targets, phospholipid diselenide polyethylene glycol, phospholipids, cholesterol, and neutral fat. According to the needleless percutaneous injection composition, a response type cell membrane is obtained by mixing a hyperplastic scar fiber cell membrane, a keloid fiber cell membrane and a phospholipid diselenide bond polyethylene glycol, and after targeting and positioning to an affected part, active ingredients are released in a manner of combining burst release and sustained release by the mutual coordination of the phospholipid diselenide bond polyethylene glycol and a liposome, so that the blood concentration is quickly reached, long-acting treatment is maintained, the injection frequency during treatment is reduced, and the damage to skin during injection is reduced; and the fear of the needle injection to the patient can be reduced, and the compliance of the patient is improved.
Description
Technical Field
The present application relates to the field of medicine, and in particular to a composition for needleless percutaneous injection.
Background
Scar is a collective term for a series of morphological and histopathological changes in human skin after it has been subjected to a wound. The scar not only seriously affects the appearance and the image of the patient, but also greatly reduces the life quality of the patient and brings psychological and economic burden to the patient, so that the scar prevention and treatment and the medical research thereof have important social and economic values.
Currently, the most common pharmaceutical treatment for scars is glucocorticoid. Namely, the glucocorticoid medicine is injected to the affected part through an injection needle.
However, scar treatment is a lengthy procedure, and frequent injections through the needle not only result in poor patient compliance, but also can cause damage to the skin and even exacerbate the scar severity.
Disclosure of Invention
In view of the above, the present application provides a composition for needle-free transdermal injection to at least partially solve the above-mentioned problems.
In order to achieve the above purpose, the present application is realized by the following technical scheme:
in a first aspect, a composition for needleless transdermal injection of the present application comprises:
scar inhibitor, specific targeting, phospholipid diselenide polyethylene glycol, phospholipid, cholesterol and neutral fat;
the ratio of the mass of scar inhibitor to the total mass of specific target, phospholipid, cholesterol and neutral fat is 1:15-24;
the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:7-15;
the ratio of the total mass of the phospholipid, the cholesterol and the neutral fat to the mass of the specific targeting agent is 1:0.1-1;
the mass ratio of the phospholipid to the neutral fat is 1:2.5-7.5;
the mass ratio of the phospholipid to the cholesterol is 1:1.25-3;
the concentration of scar inhibitor in the composition for needleless percutaneous injection is 0.25-1mg/ml.
For the mass of scar inhibitor, the ratio of the mass to the total mass of specific targeting, phospholipids, cholesterol and neutral fat, 1:15-24 refers to any value in the range of 1:15 to 1:24, such as 1:15, 1:15.5, 1:16, 1:16.5, 1:17, 1:17.5, 1:18, 1:18.5, 1:19, 1:19.5, 1:20, 1:20.5, 1:21, 1:21.5, 1:22, 1:22.5, 1:23, 1:23.5 and 1:24.
For mass ratio of phospholipid diselenide polyethylene glycol to specific target, 1:7-15 refers to any value in the range of 1:7 to 1:15, e.g., 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10, 1:10.5, 1:11, 1:11.5, 1:12, 1:12.5, 1:13, 1:13.5, 1:14, 1:14.5, and 1:15.
For the ratio of the total mass of phospholipids, cholesterol and neutral fat to the mass of specific targeting, 1:0.1-1 refers to any value in the range of 1:0.1 to 1:1, such as 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9 and 1:1.
For a mass ratio of phospholipids to neutral fat, 1:2.5-7.5 refers to any value in the range of 1:2.5 to 1:7.5, such as 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5 and 1:7.
For the mass ratio of phospholipids to cholesterol, 1:1.25-3 refers to any value in the range of 1:1.25 to 1:3, such as 1:1.25, 1:1.4, 1:1.5, 1:1.6, 1:1.8, 1:2, 1:2.1, 1:2.2, 1:2.4, 1:2.6, 1:2.7, 1:2.8, 1:2.9, and 1:3.
For the concentration of scar inhibitor, 0.25-1mg/ml refers to any value in the range of 0.25mg/ml to 1mg/ml, such as 0.25mg/ml, 0.3mg/ml, 0.35mg/ml, 0.4mg/ml, 0.45mg/ml, 0.5mg/ml, 0.55mg/ml, 0.6mg/ml, 0.65mg/ml, 0.7mg/ml, 0.75mg/ml, 0.8mg/ml, 0.85mg/ml, 0.9mg/ml, 0.95mg/ml, and 1mg/ml.
Preferably, the specific targets comprise: a proliferative scar fibroblast membrane and/or a keloid fibroblast membrane.
When the specific target comprises a hypertrophic scar fibrous cell membrane and a keloid fibrous cell membrane, the mass ratio of the hypertrophic scar fibrous cell membrane to the keloid fibrous cell membrane is 1:1.
In particular, the specific target may be a single substance, such as a hypertrophic scar fibroblast membrane, or a keloid fibroblast membrane. The specific target may also be a composition, such as a composition of a hypertrophic scar fibroblast membrane and a keloid fibroblast membrane.
When the specific target is a composition consisting of a hypertrophic scar fibroblast and a keloid fibroblast, the mass ratio of the hypertrophic scar fibroblast to the keloid fibroblast is 1:1.
It should be noted that the hypertrophic scar fibroblast membrane refers to the cell membrane of the hypertrophic scar fibroblast. Similarly, keloid fibroblast membrane refers to the cell membrane of keloid fibroblasts.
Preferably, the scar inhibitor comprises: triamcinolone acetonide or betamethasone.
Preferably, the phospholipid comprises: electronegative phospholipids and ampholytic phospholipids;
the mass ratio of electronegative phospholipids to ampholytic phospholipids is 1:0.25-0.5.
For mass ratios of electronegative phospholipids to ampholytic phospholipids, 1:0.25-0.5 refers to any value in the range of 1:0.25 to 1:0.5, such as 1:0.25, 1:0.27, 1:0.29, 1:0.3, 1:0.32, 1:0.34, 1:0.35, 1:0.36, 1:0.38, 1:0.4, 1:0.42, 1:0.44, 1:0.45, 1:0.46, 1:0.48, 1:0.49, and 1:0.5.
Preferably, when the electronegative phospholipid is distearoyl phosphatidylethanolamine and the ampholytic phospholipid is soybean lecithin, the neutral fat comprises glycerol trioleate.
Electronegative phospholipid means a negatively charged phospholipid. Ampholytic phospholipids refer to phospholipids comprising two hydrophilic and hydrophobic moieties that differ in nature.
Preferably, the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:10.
The preparation method of the composition for needleless percutaneous injection comprises the following steps:
dissolving cholesterol, phospholipid and neutral fat in organic solvent to obtain oil phase.
Specifically, the organic solvent for dissolving cholesterol, phospholipids and neutral fat may be chloroform, diethyl ether, or a mixture of chloroform and diethyl ether, but is not limited thereto.
Dissolving the active ingredients, and mixing with the oil phase to obtain colostrum.
Specifically, when the active ingredient is triamcinolone acetonide, the triamcinolone acetonide can be added into the oil phase and uniformly mixed to obtain colostrum; when the active ingredient is betamethasone, the betamethasone and the sodium chloride solution or the glucose solution or the combination of the two can be mixed evenly. And adding the betamethasone water solution into the oil phase, and uniformly mixing to obtain the colostrum. The osmotic pressure of the sodium chloride solution and the glucose solution for dissolving the betamethasone is 275-285mmol/L. The osmotic pressure of the sodium chloride solution and the glucose solution is any value in the range of 275-285mmol/L, such as 275mmol/L, 280mmol/L, and 285mmol/L.
Adding colostrum into injectable water, and stirring to obtain multiple emulsion. And carrying out vacuum drying treatment on the compound emulsion to obtain liposome solid.
Adding water for injection into liposome solid to obtain liposome solution.
Obtain the proliferation scar fibroblast membrane and keloid fibroblast membrane, and obtain the specific target.
Specifically, the hypertrophic scar fibroblast and keloid fibroblast may be obtained by centrifuging hypertrophic scar fibroblast and keloid fibroblast, dispersing the centrifuged hypertrophic scar fibroblast and keloid fibroblast into phosphate buffer salt solution (pH 7.4) containing 0.1% protein inhibitor, and ultrasonic crushing the heavy suspension. Sequentially performing centrifugation to obtain cell membranes. Sequentially re-suspending the cell membrane in phosphate buffer salt solution to obtain hypertrophic scar fibroblast membrane and keloid fibroblast membrane. Wherein the phosphate buffer solution at the time of resuspension does not contain protease inhibitor of ethylenediamine tetraacetic acid.
Mixing the specific target with phospholipid diselenide polyethylene glycol, and homogenizing to obtain a mixture.
Specifically, the specific targeting substance and the polyethylene glycol with the phospholipid diselenide bond are homogenized, so that a mixture with uniform particles and smaller particle size can be obtained.
Adding the mixture into liposome solution, incubating, sequentially centrifuging, and re-dispersing the centrifuged precipitate to obtain the composition for needleless percutaneous injection.
Specifically, the precipitate after centrifugation may be redispersed by adding the centrifuged material to water for injection to clean the unencapsulated portion and achieve redispersion.
Specifically, the centrifugation time is 5-8min, for example, 5min, 6min, 7min, and 8min.
From the above technical solutions, the present application provides a composition for needle-free percutaneous injection. The composition for needleless percutaneous injection comprises: triamcinolone acetonide/betamethasone, hypertrophic scar fibre cell membranes and keloid fibre cell membranes, phospholipid diselenide polyethylene glycol, distearoyl phosphatidylethanolamine, soybean lecithin, cholesterol, triolein and water for injection. The responsive cell membrane can be obtained by mixing the hypertrophic scar fiber cell membrane, the keloid fiber cell membrane and the phospholipid diselenide polyethylene glycol, and the active ingredients are released in a manner of combining burst release and sustained release by the mutual coordination of the phospholipid diselenide polyethylene glycol and the liposome after targeting and positioning to the affected part, so that the blood concentration is quickly reached, and meanwhile, long-acting treatment is kept, the injection frequency during treatment is reduced, and the damage to skin during injection is lightened; and the fear of the needle injection to the patient can be reduced, and the compliance of the patient is improved.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph of quality inspection results for each prescription provided in example 2 of the present application;
FIG. 2 is a graph showing the results of examining the amounts and types of phospholipids provided in example 3 of the present application;
FIG. 3 is a graph showing the results of examining the amount of cholesterol used in example 4 of the present application;
FIG. 4 is a view showing the results of examining the type and amount of neutral fat as provided in example 5 of the present application;
FIG. 5 is a plot of the amount of specific targeting provided in example 6 of the present application;
FIG. 6 is a graph showing the results of examining the amount of polyethylene glycol having a phospholipid diselenide bond in example 7 of the present application;
FIG. 7 is the results of an in vitro hemolysis assay provided in example 8 of the present application;
FIG. 8 is the results of an in vitro release test provided in example 9 of the present application;
fig. 9 is the results of the anti-rabbit ear scar test provided in example 10 of the present application.
Description of the embodiments
In order to better understand the technical solutions in the embodiments of the present application, the following description will clearly and completely describe the technical solutions in the embodiments of the present application with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only some embodiments of the present application, but not all embodiments. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments provided herein shall fall within the scope of the embodiments of the present application.
The present application is further described below with reference to specific examples.
Example 1: prescription information
The amounts of each formulation when the active ingredients are betamethasone and triamcinolone acetonide, respectively, are listed in example 1, with specific information as shown in table 1 below:
table 1 prescription information
Example 2: quality inspection
Example 2 samples of formulations 1 to 6 of example 1 were examined for encapsulation efficiency, in vitro release, cell activity, as shown in fig. 1 and table 2:
table 2 quality inspection of prescriptions
By examining the encapsulation efficiency, in vitro release, cell activity of the samples of formulas 1 to 6, it can be seen that:
the encapsulation rate of the samples of prescriptions 1 to 6 is not lower than 90%, which indicates that more active ingredients can be encapsulated in the carrier system of 6 prescription samples, and the loss of the active ingredients can be reduced.
In the in vitro release investigation of samples of prescriptions 1 to 6 for 72 hours, more than 90% of active ingredients can be released from 6 prescription samples, which indicates that the sample system is beneficial to improving the utilization rate of the active ingredients.
In the cell activity investigation of the samples of the prescriptions 1 to 6, the cell activity of the 6 prescriptions is lower than 80%, which indicates that the 6 prescriptions can effectively inhibit cell proliferation and reduce scar tissue generation.
Example 3: investigation of the amount and type of Phospholipids
The amount and type of phospholipids used in this test were examined using the sample of prescription 5 of example 1 as a control, and the specific contents are shown in fig. 2 and table 3:
TABLE 3 examination of the amounts and types of phospholipids
In example 3, the amount and type of the phospholipid were examined, and as shown in fig. 2, it can be seen from the test results that the type and amount of the phospholipid have an effect on the encapsulation efficiency of the sample, specifically, the following:
in formula 5-1, liposome was prepared using dioleoyl phosphatidylethanolamine and egg yolk lecithin, wherein the mass parts of dioleoyl phosphatidylethanolamine were the same as that of distearoyl phosphatidylethanolamine in formula 5, and the mass parts of soybean lecithin were the same as that of egg yolk lecithin in formula 5. As can be seen from the encapsulation efficiency, the liposome prepared from dioleoyl phosphatidylethanolamine and egg yolk lecithin had a poor encapsulation efficiency compared to formulation 5, and the formulation 5-1 sample did not encapsulate the active ingredient well.
Liposomes were prepared using only dioleoyl phosphatidylethanolamine in formulation 5-2, with samples having significantly lower encapsulation rates than 90%, indicating that the encapsulation of the active ingredient is not satisfactory using only dioleoyl phosphatidylethanolamine.
The distearoyl phosphatidyl ethanolamine and soybean lecithin of prescription 5-3 are used in small amounts, which is unfavorable for forming liposome and results in low encapsulation efficiency. The distearoyl phosphatidyl ethanolamine and soybean lecithin of prescription 5-4 are too high in dosage, and are also unfavorable for liposome, thereby affecting encapsulation.
When the prescription 5 sample is examined, the encapsulation rate can reach 90%, which shows that the prescription sample can well encapsulate the active ingredients and reduce the loss of the active ingredients.
Example 4: investigation of cholesterol usage
The test uses the sample of the prescription 5 of the example 1 as a control, and the cholesterol consumption is examined, and the specific contents are shown in fig. 3 and table 4:
TABLE 4 investigation of cholesterol usage
Example 4 the amount of cholesterol was examined and shown in figure 3.
No cholesterol was added to the formulations 5-5, and the sample showed poor encapsulation and severe loss of active ingredient. In the formulations 5-6, the encapsulation efficiency still does not reach 90% because the excessive amount of cholesterol affects the balance of the system.
Example 5: investigation of neutral fat type and amount
The test uses the prescription 5 sample of example 1 as a control to examine the type and amount of the neutral fat, and the specific contents are shown in fig. 4 and table 5:
table 5 screening and dose investigation of neutral fat
Example 5 the type and amount of neutral fat were examined, and as shown in fig. 4, it was found from the test results that the type and amount of neutral fat had a large influence on the degree of polymer dispersion of the sample.
In formulations 5-7, the same mass parts of palmitic acid triglyceride as the triolein in formulation 5 was used to prepare the samples, but the polymer dispersion index of the formulations 5-7 samples was as high as 0.3, indicating that the use of palmitic acid triglyceride was detrimental to system dispersion. The system dispersibility of the prescription 5 using triolein is close to 0.1, which shows that the system dispersibility is better, the agglomeration tendency is smaller, and the system uniformity is better, thereby being more beneficial to the release of the active ingredients.
The polymer dispersibility index of the formulations 5-8 is close to 3, which indicates that the too small dosage of triolein is unfavorable for system dispersion; the polymer dispersibility index of formulas 5-9 is similar to 3, but the large amount of triolein in formulas 5-9 indicates that excessive amount of triolein can cause system coagulation, resulting in poor system uniformity and thus being unfavorable for the release of active ingredients.
Example 6: investigation of the amount of specific targeting
The test uses the sample of the prescription 5 of the example 1 as a control to examine the amount of the hypertrophic scar fibroblast and keloid fibroblast, and the specific contents are shown in fig. 5 and table 6:
TABLE 6 investigation of specific targeting amounts
Example 6 is an examination of the amount of hypertrophic scar fibroblast and keloid fibroblast used. As shown in fig. 5.
The amounts of the hypertrophic scar fibroblast and keloid fibroblast in prescription 5-10, prescription 5 and prescription 5-11 are gradually increased. Experiments show that the scar detention rate of the prescription 5-10 is low, which indicates that the dosage of the hypertrophic scar fibroblast and the keloid fibroblast is low, and the detention of the active ingredients at the scar is not facilitated, so that the targeting and positioning of the affected part are not facilitated.
The scar retention rates of prescription 5 and prescription 5-11 are equal, not less than 70%, indicating that both prescription 5 and prescription 5-11 are beneficial for the active ingredient to remain in the scar. However, the amount of the hypertrophic scar fiber cell membrane and the keloid fiber cell membrane in the prescription 5-11 is close to 2 times of the amount of the hypertrophic scar fiber cell membrane and the keloid fiber cell membrane in the prescription 5, which easily causes relatively larger granularity of the system and is unfavorable for drug release.
Example 7: investigation of the amount of polyethylene glycol with double selenium bonds in the Phospholipids
The test uses the sample of the prescription 5 of the example 1 as a control, and examines the dosage of the phospholipid diselenide polyethylene glycol, and the specific content is shown in fig. 6 and table 7:
TABLE 7 investigation of the amount of polyethylene glycol used in phospholipid diselenide linkage
Example 7 is an examination of the amount of polyethylene glycol with a phospholipid diselenide bond, as shown in FIG. 6.
No phospholipid diselenide polyethylene glycol is added in the prescription 5-12, so that the prescription 5-12 sample has no burst release effect, so that the in-vitro release is low at 2 hours, and the inhibition of scar tissues is not facilitated. In the prescription 5-14, although the phospholipid diselenide polyethylene glycol is added, the dosage is small, the in vitro release is relatively low, the burst release effect of the active ingredient is not obvious, and the inhibition of scar tissues is also not facilitated.
In vitro release of prescription 5 and prescription 5-13 are basically consistent, but the dosage of the phospholipid diselenide polyethylene glycol in prescription 5-13 is higher, which is easy to cause poor uniformity of system particles, so that the dosage of the phospholipid diselenide polyethylene glycol in prescription 5 is relatively more reasonable.
Example 8: in vitro hemolysis test
Test sample: sample of recipe 5 in example 1.
Taking a blood sample of the rabbit ear vein of a healthy family, taking out fibrin by light stirring, adding a PBS solution, centrifuging, discarding the supernatant, and repeating the above operation for 4-5 times until the supernatant is basically free of obvious red. And diluting the obtained red blood cells with PBS solution to obtain a red blood cell suspension for later use.
Three equal portions of erythrocyte suspension were taken:
preparation of negative control group (PBS): adding a PBS solution to the first aliquot of red blood cell suspension;
preparation of positive control group (deionized water): adding deionized water to the second portion of the red blood cell suspension;
preparation of the sample set to be tested (prescription 5): adding the sample of prescription 5 to a third suspension of erythrocytes;
the negative control group, the positive control group and the sample group to be tested were incubated at 37℃for 4h and centrifuged. The supernatants of each group were individually taken in 96-well plates, absorbance was measured by an enzyme-labeled instrument (λ=570 nm) and the hemolysis rate was calculated.
As shown in fig. 7, the hemolysis rate of deionized water (positive control group) is close to 100%, the hemolysis rate of PBS solution (negative control group) is close to 0%, the hemolysis rate of the sample of prescription 5 is lower than <5%, which indicates that the sample of prescription 5 has almost no hemolysis on rabbit red blood cells, and the safety is good.
Example 9: in vitro Release test
Test sample: sample of recipe 5 in example 1.
Preparation of the sample set to be tested (prescription 5): the prescription 5 sample was placed in a dialysis bag. After the packaging, the mixture is placed into a centrifuge tube, and isotonic physiological saline is filled in the centrifuge tube.
Preparation of the original drug group: triamcinolone acetonide in an amount equivalent to the active ingredient of formula 5 of example 1 was placed in a dialysis bag. After the packaging, the mixture is placed into a centrifuge tube, and isotonic physiological saline is filled in the centrifuge tube.
The sample set and the drug substance set to be tested were oscillated at a constant speed (100 rpm) in a shaker at 37 ℃. The solution outside the dialysis bag was taken at the time points of 30min, 1h, 2h, 6h, 9h, 12h, 24h, 36h, 48h and 72h, respectively, and the equivalent amount of isotonic physiological saline was supplemented.
And measuring the concentration of the active ingredient dissolved at each time point of the sample group to be measured and the original medicine group, and calculating the in vitro release rate.
As shown in fig. 8, the outer layer of the sample group to be tested (prescription 5) is a cell membrane capable of sensing and responding to changes in the level of active oxygen (hypertrophic scar fibrous cell membrane and keloid fibrous cell membrane), and the inner layer is a liposome having a sustained release property. The hypertrophic scar fibroblast membrane and keloid fibroblast membrane carry active ingredients, and after needleless injection into the scar, corresponding cells can be targeted in a short time, the carried active ingredients can be quickly released in response to the microenvironment of higher active oxygen in the scar, and then the liposome inside is released to stabilize and slowly release the active ingredients. The distearoyl phosphatidylethanolamine is matched with the liposome, so that the solubility of the active ingredient can be improved, and the in-vitro release is relatively high.
However, triamcinolone acetonide in the drug substance group has low in vitro release due to its lack of cell membranes capable of sensing and responding to changes in active oxygen levels and its non-liposomal form, which is poor in solubility.
Example 10: anti-rabbit ear scar test
New Zealand rabbits were randomly equally divided into normal skin, no treatment, needle injection, needle-free injection and commercial groups.
The rabbit ear ventral scar model was established for New Zealand rabbits in the no-treatment, needle-injected, needleless, and commercially available groups.
The sample of prescription 5 in example 1, 20mg/ml, was injected into the needle injection group by means of a needle syringe (disposable syringe with needle).
The sample of prescription 5 in example 1 was injected into the needleless injection group by a needleless injector at 20 mg/ml.
The commercial group was injected with a commercial triamcinolone acetonide injection via a needle syringe.
Wherein the administration amounts and the administration concentrations of the needle-containing injection group, the needleless injection group and the commercial group are consistent.
Injections were continued 2 times at 1 week intervals. The scar efficacy was evaluated after one week post injection 2. The thickness of the blood stasis tissue and normal skin dermis in hematoxylin-eosin tissue sections was measured and the epilepsy index was calculated.
As shown in fig. 9, the scar index was significantly increased in the untreated group without any treatment after modeling compared to the normal skin group. The scar index was relatively higher in the needle-injected, needleless and commercially available groups compared to the normal skin group after treatment, but significantly lower in the non-treated group.
Since the needle-injected group and the commercial group were administered using a syringe with an injection needle, the scar index was still high in both groups compared to the needleless injection group. Thus, needle injections can be seen to cause some damage to tissue.
As can be seen from fig. 9, the needle-injected group and the needleless injected group have a better scar-inhibiting effect, but the scar-inhibiting effect is more remarkable by the administration of needleless injection.
It should also be noted that the term "comprises," "comprising," or any other variation thereof is intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising at least one of the elements" does not exclude the presence of additional identical elements in a process, method, article or apparatus that comprises the element.
In this specification, each embodiment is described in a progressive manner, and identical and similar parts of each embodiment are all referred to each other, and each embodiment mainly describes differences from other embodiments.
Finally, it should be noted that the foregoing description is only an example of the present application, and is merely for illustrating the technical solution of the present invention, not for limiting the present application. Various modifications and changes may be made to the present application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc. which are within the spirit and principles of the present application are intended to be included within the scope of the claims of the present application.
Claims (7)
1. A composition for needle-free transdermal injection comprising:
scar inhibitor, specific targeting, phospholipid diselenide polyethylene glycol, phospholipid, cholesterol and neutral fat;
the ratio of the mass of the scar inhibitor to the total mass of the specific targeting agent, the phospholipid, the cholesterol and the neutral fat is 1:15-24;
the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:7-15;
the ratio of the total mass of the phospholipid, the cholesterol and the neutral fat to the mass of the specific targeting agent is 1:0.1-1;
the mass ratio of the phospholipid to the neutral fat is 1:2.5-7.5;
the mass ratio of the phospholipid to the cholesterol is 1:1.25-3;
the concentration of the scar inhibitor in the composition for needleless percutaneous injection is 0.25-1mg/ml.
2. The composition for needle-free transdermal injection according to claim 1, wherein,
the specific targets include: a proliferative scar fibroblast membrane and/or a keloid fibroblast membrane.
3. The composition for needle-free transdermal injection according to claim 2, wherein,
when the specific target comprises the hypertrophic scar fibroblast membrane and the keloid fibroblast membrane, the mass ratio of the hypertrophic scar fibroblast membrane to the keloid fibroblast membrane is 1:1.
4. The composition for needle-free transdermal injection according to claim 1, wherein,
the scar inhibitor comprises: triamcinolone acetonide or betamethasone.
5. The composition for needle-free transdermal injection according to claim 1, wherein,
the phospholipid comprises: electronegative phospholipids and ampholytic phospholipids;
the mass ratio of the electronegative phospholipid to the ampholytic phospholipid is 1:0.25-0.5.
6. The composition for needle-free transdermal injection according to claim 5, wherein,
when the electronegative phospholipid is distearoyl phosphatidylethanolamine and the ampholytic phospholipid is soybean lecithin, the neutral fat comprises glycerol trioleate.
7. The composition for needle-free transdermal injection according to any one of claim 1 to 6,
the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:10.
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2682038A1 (en) * | 1991-10-08 | 1993-04-09 | Patrinove | Intracellular vesicular vectors and their cosmetic applications |
WO2002076508A1 (en) * | 2001-03-22 | 2002-10-03 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
WO2004047792A2 (en) * | 2002-11-24 | 2004-06-10 | Novosom Ag | Liposomal glucocorticoids |
CN104173285A (en) * | 2013-05-23 | 2014-12-03 | 上海市第七人民医院 | Preparation method for triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent and application to target hypertrophic scars |
CN114732787A (en) * | 2021-12-30 | 2022-07-12 | 上海中医药大学 | Cross-linked cyclodextrin metal-organic framework quercetin-loaded nano-drug particle and application thereof |
CN114831939A (en) * | 2021-01-30 | 2022-08-02 | 南京星银药业集团有限公司 | Triamcinolone acetonide acetate composition spray and preparation method thereof |
CN114848597A (en) * | 2022-07-11 | 2022-08-05 | 北京中科利华医药研究院有限公司 | Sodium thiosulfate injection packaged by double-chamber bag and application |
-
2023
- 2023-12-08 CN CN202311681459.8A patent/CN117357480B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2682038A1 (en) * | 1991-10-08 | 1993-04-09 | Patrinove | Intracellular vesicular vectors and their cosmetic applications |
WO2002076508A1 (en) * | 2001-03-22 | 2002-10-03 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
WO2004047792A2 (en) * | 2002-11-24 | 2004-06-10 | Novosom Ag | Liposomal glucocorticoids |
CN104173285A (en) * | 2013-05-23 | 2014-12-03 | 上海市第七人民医院 | Preparation method for triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent and application to target hypertrophic scars |
CN114831939A (en) * | 2021-01-30 | 2022-08-02 | 南京星银药业集团有限公司 | Triamcinolone acetonide acetate composition spray and preparation method thereof |
CN114732787A (en) * | 2021-12-30 | 2022-07-12 | 上海中医药大学 | Cross-linked cyclodextrin metal-organic framework quercetin-loaded nano-drug particle and application thereof |
CN114848597A (en) * | 2022-07-11 | 2022-08-05 | 北京中科利华医药研究院有限公司 | Sodium thiosulfate injection packaged by double-chamber bag and application |
Non-Patent Citations (1)
Title |
---|
邓玉萍等: "醋酸曲安奈德柔性纳米脂质体的制备及瘢痕皮肤的透皮特性", 中国医院药学杂志, vol. 34, pages 1 - 4 * |
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