CN1762488A - Externally applied medicinal composition of human cell fibronectin and preparation method thereof - Google Patents
Externally applied medicinal composition of human cell fibronectin and preparation method thereof Download PDFInfo
- Publication number
- CN1762488A CN1762488A CN 200510018079 CN200510018079A CN1762488A CN 1762488 A CN1762488 A CN 1762488A CN 200510018079 CN200510018079 CN 200510018079 CN 200510018079 A CN200510018079 A CN 200510018079A CN 1762488 A CN1762488 A CN 1762488A
- Authority
- CN
- China
- Prior art keywords
- applied medicinal
- externally
- human cellular
- medicinal composition
- fibronectin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000016359 Fibronectins Human genes 0.000 title claims abstract description 62
- 108010067306 Fibronectins Proteins 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title claims description 21
- 210000005260 human cell Anatomy 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 238000004113 cell culture Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims abstract 2
- 230000001413 cellular effect Effects 0.000 claims description 41
- 239000000758 substrate Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 17
- 239000000843 powder Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 13
- 239000008215 water for injection Substances 0.000 claims description 13
- 239000000865 liniment Substances 0.000 claims description 11
- 229940040145 liniment Drugs 0.000 claims description 11
- 239000000499 gel Substances 0.000 claims description 9
- 239000007921 spray Substances 0.000 claims description 7
- 239000000872 buffer Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000003860 storage Methods 0.000 claims description 6
- 230000002421 anti-septic effect Effects 0.000 claims description 5
- 235000011187 glycerol Nutrition 0.000 claims description 5
- 239000000017 hydrogel Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 239000007951 isotonicity adjuster Substances 0.000 claims description 4
- 230000007774 longterm Effects 0.000 claims description 4
- 239000006071 cream Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000006072 paste Substances 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 238000005057 refrigeration Methods 0.000 claims 1
- 206010052428 Wound Diseases 0.000 abstract description 14
- 208000027418 Wounds and injury Diseases 0.000 abstract description 14
- 206010028980 Neoplasm Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 6
- 239000011159 matrix material Substances 0.000 abstract description 6
- 208000025865 Ulcer Diseases 0.000 abstract description 4
- 208000006374 Uterine Cervicitis Diseases 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 4
- 206010008323 cervicitis Diseases 0.000 abstract description 4
- 231100000397 ulcer Toxicity 0.000 abstract description 4
- 230000008378 epithelial damage Effects 0.000 abstract description 3
- 238000001356 surgical procedure Methods 0.000 abstract description 3
- 208000014674 injury Diseases 0.000 abstract description 2
- 230000008733 trauma Effects 0.000 abstract description 2
- 241000255580 Ceratitis <genus> Species 0.000 abstract 1
- 239000012634 fragment Substances 0.000 abstract 1
- 230000037380 skin damage Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 15
- 238000012360 testing method Methods 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 210000002381 plasma Anatomy 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000004321 preservation Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 5
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 5
- 229960002216 methylparaben Drugs 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 230000001954 sterilising effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000007789 sealing Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000028990 Skin injury Diseases 0.000 description 3
- 206010053615 Thermal burn Diseases 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 206010023332 keratitis Diseases 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000002271 resection Methods 0.000 description 3
- 206010072170 Skin wound Diseases 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 244000309465 heifer Species 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000004493 neutrocyte Anatomy 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides an externally-used pharmaceutical composition which is prepared from human cell fibronectin and/or fragment as reactive component through cell cultivation method as well as externally used matrix. The externally-used pharmaceutical composition can be applied locally to treat various skin damage, trauma and ulcer, burns, wounds after cancer excision surgery, and epithelium damage diseases such as ceratitis and cervicitis.
Description
Technical field
The present invention relates to externally-applied medicinal composition of a kind of Human Cellular Fibronectin (Human Cellular Fibronectin) and preparation method thereof.More particularly, the present invention relates to a kind of Human Cellular Fibronectin and/or its segment is active component, with the compositions of external-use substrate composition.Local treatment various skin injurys, wound and the ulcer used of externally-applied medicinal composition of the present invention; Burn and scald, beauty treatment; Be used for the face of hindering behind the cancer resection surgery; Epithelial damage diseases such as treatment keratitis, cervicitis.
Background technology
(Fibronectin FN) is the macromole glycoprotein that the intravital class of vertebrates has the various biological function to fibronectin.Fibronectin mainly contains two types, promptly the blood plasma fibronectin (Plasm Fibronectin, pFN) and cell fibronectin (Cellular Fibronectin, cFN).The distribution of two class fibronectins, molecular structure and biological function have tangible different.
The dimer that the blood plasma fibronectin is made up of two polypeptide chains is present in solvable type in the body fluid such as blood plasma, amniotic fluid, seminal fluid, cerebrospinal fluid.Cell fibronectin is made up of dimer or polymer, is present in cell surface, extracellular matrix or the basement membrane with the microfibrous or the impalpable structure of insoluble type.
The domain that does not contain EDA, EDB in the molecular structure of blood plasma fibronectin has only a subunit to contain variable region IIICS in its dimer.Contain different EDA of quantity and/or EDB domain in the molecular structure of the fine even egg of cell, its all subunits all contain variable region IIICS.
The blood plasma fibronectin has opsonification, and the chemistry effect of tending to act participates in hemostasis, promotes wound healing, and is relevant with the differentiation and the tumor of cell.The fine egg that connects of cell has adhesive capacity, keeps the cell normal configuration, participates in cell movement, promotes cell division, plays an important role in fetal development, tumor generation and pathophysiological processes such as transfer and repair in trauma.
At present, people just extract acquisition blood plasma fibronectin and study from animal blood such as Sanguis Bovis seu Bubali or human blood, especially for treatment burn, wound (Grinnel F.J cell Biol, 1984; 26:107), keratitis, cervicitis etc. (NishidaT, etal.Arch ophthalmol, 1984,102:455) disease has significant curative effect.The recurrence of also finding tumor is relevant closely with fibronectin with transfer, has test to show that fibronectin and/or segment have tangible antitumaous effect (Yi M, Proc NatlAcad Sci USA; 2001,98 (2): 620).
But the blood plasma fibronectin is as a kind of blood products, and it may carry virus or pollutant, as the crazy heifer disease virus of Sanguis Bovis seu Bubali, human blood hepatitis B, hepatitis C, syphilis, AIDS etc.Therefore, great unsafe factor is arranged, also be subjected to the limitation of resource simultaneously with blood plasma fibronectin treatment disease.This becomes the blood plasma fibronectin and is difficult to widely used major obstacle.
It is more difficult to extract cell fibronectin from animal tissue.Therefore, research of cell fibronectin for a long time and more difficult the carrying out of application.Along with development of biology, people can pass through the separation of human somatic cell, and the pedestrian worker that goes forward side by side cultivates, and prepare Human Cellular Fibronectin through extraction, purification.It can not only prepare in a large number, is not subjected to resource limit; And the more important thing is the generation of avoiding the haematogenous infectious disease, and applying clinical has better homology.
Human Cellular Fibronectin is unsettled as a kind of activated protein at normal temperatures, particularly easier degeneration or degraded in aqueous medium, and make its loss of bioactivity.For research and the application of carrying out Human Cellular Fibronectin, particularly can satisfy the application requirements of clinical relevant indication, be starved of a kind of suitable dosage form.This dosage form not only requires good stability, energy Long-term Storage, easy to use, and can fully demonstrate biological activity.
Summary of the invention
The object of the present invention is to provide the exterior-applied formulation of Human Cellular Fibronectin, suitable various skin injurys, wound and the ulcer of being used for the treatment of clinically; Burn and scald, beauty treatment; Be used for the face of hindering behind the cancer resection surgery; Epithelial damage diseases such as treatment keratitis, cervicitis.
The inventor has carried out a large amount of research, filters out exterior-applied formulation, and the prescription of preparation and preparation technology have not only satisfied the application of above-mentioned indication in treatment, and good stability, can Long-term Storage, easy to use, and demonstrate good curative effect.Thus, finished the present invention.
The present invention relates to a kind of externally-applied medicinal composition, it comprises the pharmaceutical composition that Human Cellular Fibronectin and/or its segment are formed as active component and external-use substrate.
The form of externally-applied medicinal composition of the present invention comprises: solution, spray, lotion, liniment, glycerin, paste, cream, ointment, gel, liniment, membrane.
It is more suitable to be mixed with spray when being used for the treatment of skin injury, wound, ulcer, burn and scald clinically, and it not only makes Human Cellular Fibronectin be evenly distributed on damage zone, and can not smear because of friction damage zone and to cause physical stimulation.Spray-type also is adapted to use in the wound after the surgical resection cancerous tissue, existing hemostasis, promotes the effect of wound healing, can suppress the postoperative recurrence of cancer again.
Active component Human Cellular Fibronectin among the present invention, it comprises Human Cellular Fibronectin and/or its segment.Human Cellular Fibronectin is the complete molecule of being made up of the polypeptide chain more than 2 or 2; The segment of Human Cellular Fibronectin is the degraded segment of complete molecule, and it includes active structure domain, has biological function equally.
Human Cellular Fibronectin among the present invention and/or segment are by the cultivation of people's cell, separation and Extraction, the refining acquisition.Content in compositions with total restatement of preparation in 0.001mg/g to 10mg/g scope, preferred content with total restatement of preparation in 0.1mg/g to 2mg/g scope.
External-use substrate among the present invention comprises hydrogel, buffer agent, isotonic agent, antiseptic and solvent.
Hydrogel among the present invention includes carbopol (carbomer), polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, polyacrylic resin, cellulose and derivant thereof, Pa Luoshamu.
Buffer agent among the present invention includes phosphate buffer, acetate buffer, Tris-HCL buffer agent, keeps PH in 4 to 9 scope in compositions, is preferably 6 to 8 scope.
Isotonic agent among the present invention includes sodium chloride.
Antiseptic among the present invention includes methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, penicillin, streptomycin.
Solvent among the present invention includes water, glycerol, propylene glycol, ethanol.
The consumption of employed various hydrogels, buffer agent, isotonic agent, antiseptic and solvent among the present invention needs according to the dosage form for preparing, consumption preparation routinely.
The preparation method of externally-applied medicinal composition of the present invention is as follows:
(1) preparation Human Cellular Fibronectin freeze dried powder: sodium chloride and buffer agent are dissolved in the proper amount of water for injection, and mix with Human Cellular Fibronectin and/or segment solution, be distributed into the Human Cellular Fibronectin that every bottle of content is ormal weight then, make aseptic freeze-dried powder through vacuum lyophilization.
(2) preparation external-use substrate: with dissolution with solvents or swelling, the sterile solution or the semisolid matrix of ormal weight made in packing with antiseptic and/or hydrogel.
(3) storage before using: the Human Cellular Fibronectin freeze dried powder is in low temperature-10 ℃～-20 ℃ of following cold preservations, and effect duration is 2 years.External-use substrate low temperature-10 ℃～-20 ℃ down or room temperature storages, effect duration is 2 years.
(4) preparation of Shi Yonging: the Human Cellular Fibronectin freeze dried powder is mixed with water for injection or external-use substrate, be mixed with needed dosage form.Matching while using, or cold preservation is in a short time used after the preparation.
The specific embodiment
Following embodiment further specifies the present invention.But, be to be understood that the present invention is limited to these examples never in any form.
Embodiment 1
The preparation of Human Cellular Fibronectin freeze dried powder
Human Cellular Fibronectin 0.1g
Sodium chloride 0.88g
Dibastic sodium phosphate 0.14g
20% phosphoric acid is an amount of
Water for injection is an amount of
Total amount 100g
With sodium chloride, dibastic sodium phosphate is dissolved in an amount of water for injection, behind 20% phosphoric acid regulator solution PH, it is sterilized, and mixes with the solution of sterilizing after filtration in water for injection with Human Cellular Fibronectin, obtains 100g solution.Be sub-packed in then in the bottle of sterilization, every bottle of packing 1g becomes dry powder through vacuum lyophilization, and sealing promptly gets the Human Cellular Fibronectin freeze dried powder.This freeze dried powder, the content of Human Cellular Fibronectin is 1mg in every bottle ,-10 ℃～-20 ℃ temperature stored refrigerated, effect duration is 2 years.
Embodiment 2
The use preparation of Human Cellular Fibronectin freeze dried powder
It is the Human Cellular Fibronectin freeze dried powder bottle of 1mg that water for injection 2ml is injected content, and jolting makes dissolving gently, is the clear solution of the visible insoluble matter of no naked eyes, promptly obtains the solution that concentration is 0.5mg/ml.According to clinical need or drip a certain amount of spraying of above-mentioned solution to be coated onto use the position.This solution can disposablely use up, and also cold preservation was used in one month at low temperatures.
Embodiment 3
The preparation of fluid matrix
Acritamer 940 0.08g
Sodium hydroxide is an amount of
Water for injection is an amount of
Total amount 100g
Acritamer 940 is added in the proper amount of water for injection, abundant swelling, with behind the PH of sodium hydrate regulator solution, the packing bottle, every bottle of 2ml, sealing, sterilization promptly gets fluid matrix.Fluid matrix is at room temperature preserved, and effect duration is 2 years.
When using fluid matrix 2ml is injected the Human Cellular Fibronectin freeze dried powder bottle of content as 1mg, jolting makes dissolving gently, is the clear solution of the visible insoluble matter of no naked eyes, promptly obtains the solution that concentration is 0.5mg/ml.According to clinical need or drip a certain amount of spraying of above-mentioned solution to be coated onto use the position.This solution can disposablely use up, and also cold preservation was used in one month at low temperatures.
Embodiment 4
The preparation of gel substrate
Acritamer 940 1g
Propylene glycol 20g
Methyl parahydroxybenzoate 0.2g
Triethanolamine is an amount of
Water for injection is an amount of
Total amount 100g
Methyl parahydroxybenzoate is dissolved in the proper amount of water for injection, adds Acritamer 940 and make abundant swelling, add propylene glycol, after slowly adding triethanolamine under the restir and regulating PH, promptly get thick gel substrate 100g.Packing bottle then, every bottle of 4g, sealing, sterilization.Gel substrate is at room temperature preserved, and effect duration is 2 years.
When using gel substrate 4g is injected the Human Cellular Fibronectin freeze dried powder bottle of content as 1mg, jolting makes dissolving gently, promptly obtains the gel that concentration is 0.25mg/g.A certain amount of being applied to of above-mentioned gel need be used the position according to clinical.This gel can disposablely use up, and also cold preservation was used in one month at low temperatures.
Embodiment 5
The preparation of liniment substrate
Polyvinylpyrrolidone 5.5g
Glycerol 5g
Methyl parahydroxybenzoate 0.2g
Water for injection is an amount of
Total amount 100g
Methyl parahydroxybenzoate is dissolved in the proper amount of water for injection, adds polyvinylpyrrolidone and make abundant swelling, add glycerol, promptly get liniment substrate 100g.Packing bottle then, every bottle of 5g, sealing, sterilization.Liniment substrate is at room temperature preserved, and effect duration is 2 years.
When using liniment substrate 5g is injected the Human Cellular Fibronectin freeze dried powder bottle of content as 1mg, jolting makes dissolving gently, promptly obtains the liniment that concentration is 0.2mg/g.A certain amount of being applied to of above-mentioned liniment need be used the position according to clinical.This liniment can disposablely use up, and also cold preservation was used in one month at low temperatures.
Experiment
Human Cellular Fibronectin is to the research of Cavia porcellus wound promoting healing effect
Get Holland and plant 40 of Cavia porcelluss, body weight 200～250g, male and female half and half are divided into 2 groups at random, and promptly test group is 20,20 of matched groups.In animal abdominal part depilation, cause the wound of long 5cm with scalpel, separate wound with tweezers, visible intraperitoneal is tolerant.The wound of test group animal is with Human Cellular Fibronectin solution spray 0.5ml (including Human Cellular Fibronectin 0.25mg), conventional skin suture, and gauze is bound up a wound, for three days on end spray delivery.The wound of control animals physiological saline solution solution spray 0.5ml, other operations are identical with test group.Observe the variation of wound location in continuous 15 days and judge curative effect.In the wound 10 days healing and do not infect be produce effects; What healed and do not infect in 15 days is effectively; 15 days not the healing or wound infection be invalid.Result such as following table:
The table Human Cellular Fibronectin is to the test of Cavia porcellus wound promoting healing effect
| Group | The example number | Produce effects | Effectively | Invalid | Total effective rate (%) |
| Matched group | 20 | 5 | 8 | 7 | 65.0 |
| Test group | 20 | 12 | 7 | 1 | 95.0 |
Result of the test shows: the obvious effective rate of matched group is 25%, and the obvious effective rate of test group is 60%, two group tangible significant difference (P＜0.01).The matched group total effective rate is 65%, and the total effective rate of test group is 95%, two group significant difference (P＜0.05).Observe infection conditions, matched group has 4 zoogenetic infections, none infection of test group.Two groups of healing back optics microscopy results of wound tissue show: matched group has the fibrous tissue arrangement disorder of skim under new epithelize, a large amount of inflammatory cells (based on neutrophilic leukocyte) and a spot of macrophage are arranged; Test group has the fibrous tissue than thick-layer under new epithelize, be arranged in parallel, and blood capillary is abundant, and a large amount of inflammatory cells are arranged, and macrophage is more etc.The statistics wound healing time, test group is 9.85 ± 3.12 days, matched group is 12.85 ± 3.71 days.
The result confirms: pharmaceutical composition external surgical wound of the present invention, have tangible promotion wound healing, and reduce and infect, suppress the curative effect of pathological changes.Do not see in the test that any untoward reaction takes place.
Claims (9)
1. an externally-applied medicinal composition is characterized in that it is that active component and external-use substrate are formed that described externally-applied medicinal composition comprises with Human Cellular Fibronectin and/or segment.
2. according to the described externally-applied medicinal composition of claim 1, it is characterized in that described pharmaceutical compositions comprises: solution, spray, lotion, liniment, glycerin, paste, cream, ointment, gel, liniment, membrane.
3. according to claim 1 and 2 described externally-applied medicinal compositions, it is characterized in that described pharmaceutical compositions is a spray.
4. according to the described externally-applied medicinal composition of claim 1, it is characterized in that the active component Human Cellular Fibronectin of described externally-applied medicinal composition and/or segment are the methods by people's cell culture, through extract, the refining acquisition.
5. according to the described externally-applied medicinal composition of claim 1, it is characterized in that the active component Human Cellular Fibronectin of described external combination and/or pulsating content with total restatement of preparation in 0.001mg/g to 10mg/g scope.
6. according to claim 1 and 5 described externally-applied medicinal compositions, it is characterized in that the active component Human Cellular Fibronectin of described external combination and/or pulsating content with total restatement of preparation in 0.1mg/g to 2mg/g scope.
7. according to the described externally-applied medicinal composition of claim 1, it is characterized in that described external-use substrate comprises hydrogel, buffer agent, isotonic agent, antiseptic and solvent.
8. according to the described externally-applied medicinal composition of claim 1, it is characterized in that described pharmaceutical composition respectively with two kinds of form Long-term Storage, promptly contains the freeze dried powder and the substrate of Human Cellular Fibronectin.
9. according to claim 1 and 8 described externally-applied medicinal compositions, it is characterized in that described pharmaceutical composition is respectively with two kinds of form Long-term Storage, during use Human Cellular Fibronectin freeze dried powder and water for injection or substrate are mixed, matching while using, or preparation back term refrigeration uses.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510018079 CN1762488A (en) | 2005-10-08 | 2005-10-08 | Externally applied medicinal composition of human cell fibronectin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510018079 CN1762488A (en) | 2005-10-08 | 2005-10-08 | Externally applied medicinal composition of human cell fibronectin and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1762488A true CN1762488A (en) | 2006-04-26 |
Family
ID=36746948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510018079 Pending CN1762488A (en) | 2005-10-08 | 2005-10-08 | Externally applied medicinal composition of human cell fibronectin and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1762488A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040230A1 (en) * | 2006-09-15 | 2008-04-10 | Zhengzhou Tongyuan Biotechnology Co., Ltd. | Consolidant for trauma and ulcer comprising fibronectin |
| CN103520107A (en) * | 2013-10-11 | 2014-01-22 | 徐克之 | Foaming agent for vaginal packing |
-
2005
- 2005-10-08 CN CN 200510018079 patent/CN1762488A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040230A1 (en) * | 2006-09-15 | 2008-04-10 | Zhengzhou Tongyuan Biotechnology Co., Ltd. | Consolidant for trauma and ulcer comprising fibronectin |
| CN103520107A (en) * | 2013-10-11 | 2014-01-22 | 徐克之 | Foaming agent for vaginal packing |
| CN103520107B (en) * | 2013-10-11 | 2016-08-17 | 南京亚方药业有限公司 | A kind of vaginal plugging foam |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhou et al. | A carrier-free, dual-functional hydrogel constructed of antimicrobial peptide Jelleine-1 and 8Br-cAMP for MRSA infected diabetic wound healing | |
| JP6960333B2 (en) | A composition of micronized placental tissue optionally containing a sealant, and a method for producing and using the composition. | |
| CN102949709B (en) | A kind of external gel for treating diabetic foot and its preparation and application | |
| US10765698B2 (en) | Treatment of disease with poly-N-acetylglucosamine nanofibers | |
| CN103083226B (en) | The preparation of fibroblast growth factor-1 modifier gel and the application in diabetic foot | |
| CN107185031B (en) | A kind of biologically active medical dressing and preparation method thereof | |
| CN101472560B (en) | Medicinal composition for treating burns and preparation method thereof | |
| CN102357242B (en) | Recombination cattle alkaline fibroblast growth factor gel | |
| CN108324926B (en) | Composition of stem cell extract and antibacterial peptide and application thereof | |
| CN103159967A (en) | Preparation method of collagen-based sponge wound dressing with self-anti-inflammatory function | |
| CN114917403A (en) | Mussel-like mucin gel as well as preparation method and application thereof | |
| CN105797204A (en) | Application of chlorogenic acid in preparing wound dressing | |
| Wang et al. | Drug-loaded mesoporous polydopamine nanoparticles in chitosan hydrogels enable myocardial infarction repair through ROS scavenging and inhibition of apoptosis | |
| CN114456239A (en) | Shengtaisu and external antibacterial peptide gel preparation and application prepared therefrom | |
| CN1762488A (en) | Externally applied medicinal composition of human cell fibronectin and preparation method thereof | |
| KR101816964B1 (en) | Pharmaceutical adjuvant composition for treating damages of skin or blood vessel tissue | |
| CN102389402B (en) | Recombinant bovine basic fibroblast growth factor freeze-dried formulation for external application | |
| CN102861320B (en) | Spray for treating skin and mucosa wounds | |
| CN113143844B (en) | Polymer microneedle patch for treating acne and preparation method thereof | |
| CN109646671A (en) | A kind of growth-factor preparation and its preparation method and application | |
| RU2691144C1 (en) | Combined composition for treating infected wounds of various origins | |
| CN202191515U (en) | Composite sponge dressing | |
| CN118976097B (en) | Composition for treating gynecological diseases and preparation method and application thereof | |
| CN102362856B (en) | Recombinant bovine basic fibroblast grow factor external solution | |
| CN1290576C (en) | Thymic hormone beta 15 to promote wound healing and generation of blood |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |