CN100548370C - A kind of spray for the treatment of burns, scalds and chronic ulcer and preparation method thereof - Google Patents
A kind of spray for the treatment of burns, scalds and chronic ulcer and preparation method thereof Download PDFInfo
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- CN100548370C CN100548370C CNB2005100942032A CN200510094203A CN100548370C CN 100548370 C CN100548370 C CN 100548370C CN B2005100942032 A CNB2005100942032 A CN B2005100942032A CN 200510094203 A CN200510094203 A CN 200510094203A CN 100548370 C CN100548370 C CN 100548370C
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Abstract
The present invention relates to a kind of use and be the spray and preparation method thereof of the treatment burns, scalds and chronic ulcer of main medicinal component with PEG-haFGF PEG-aFGF.Spray Main Ingredients and Appearance and content are: the PEG-haFGF (PEG-aFGF) of 1-100 μ g/mL, 1-100mg/mL Zedoary turmeric oil, 0.001-0.05mg/mL protective agent, 0.001-0.01mg/mL antiseptic, 0.0001-0.001mg/mL stabilizing agent, 0.01-0.2mg/mL correctives, all the other are normal saline or water for injection.Said preparation has characteristics such as good stability, biological half-life is long, safety is good.
Description
Technical field
The present invention relates to a kind of liquid state that is mainly used in diseases such as treatment burn and scald, fresh wound surface, chronic ulcer, cervical erosion or the lyophilized powder spray of attached solvent in addition, specifically is to be the liquid state of main medicinal component or the lyophilizing spray of attached solvent in addition with PEG-haFGF PEG-aFGF.
Background technology
Acid fibroblast growth factor (aFGF) is the FGFs family member of second separated purification, Thomas in 1984 from Medulla Bovis seu Bubali separation and purification obtain the mixture that a polypeptide by two kinds of sizes (140Aa and 134Aa) is formed, it is a kind of wide spectrum mitogen, has 55% aminoacid sequence identical with the cationic polypeptide bFGF that is separated to from Niu Chuiti.AFGF mainly is distributed in the organ or tissues such as brain, hypophysis, nervous tissue, retina, adrenal gland, heart and bone, and other tissue content seldom is about 1/10 ~ 1/50, exists with extremely low concentration in serum and body fluid.The vivo and vitro experiment all shows, the biological effect of aFGF comprises short division effect and the active two big classes of non-short mitosin sample, wherein short division effect mainly comprises angiogenesis, organizes generation, repair in trauma and neurotrophic effect, but not short mitosin sample activity refers to the hypotension effect, regulates cell Ca
2+The adjusting of ingesting of balance, hormone secretion and participation maincenter.Bioactive pleiotropy of aFGF and neurotrophic broad spectrum activity are for clinical assurance that provides is provided from the basis for it.At present, zoopery confirms that aFGF is evident in efficacy aspect some body injury reparation and disease smelting treatment, as: aFGF can quicken the healing of burn wound; Can alleviate acute ischemia and pour into damage again and again internal organs such as liver, kidney, hearts; Participate in the reparation of spinal cord injury; Can delay and stop the further infringement of cochlear hair cell in sound damage process; Can promote the foundation of collateral circulation, but it is the same with other protein drugs, acid fibroblast growth factor aFGF also exists in the poor stability, body the half-life short and easily produce problem such as immunogenicity, by Polyethylene Glycol fixed point chemical modification method, makes above-mentioned defective obtain effective improvement.Contain three cysteine (Cys) residue in the aFGF primary structure altogether, lay respectively at the 31st, 98,
32, generally all come rock-steady structure different with the extracellular protein of many Cys of containing by forming disulfide bond, do not form disulfide bond between the Cys residue of aFGF, replace Cys with neutral amino acid as: serine (Ser), alanine (Ala), can increase the stability of aFGF to heat, acid and some proteasome degradation, simultaneously, very little to the influence of the molecular structure of aFGF and biologic activity.Because the active site of FGF mainly is positioned at the C end, modify the back to the influence that activity may cause for reducing, the 98th, 132 Cys is sported Ser, made up aFGF
Ser98,132The efficient expression engineering of mutant by ion exchange, heparin is affine two step chromatography purifications, has obtained the active and similar aFGF of natural aFGF reference substance of short Balb/c 3T3 cell increment
Ser98,132The pure product of mutant, and with mono methoxy polyethylene glycol (mPEG) 5000-maleic acid imide ester to its chemical modification of fixing a point, modified outcome is except that the short mitotic activity that has kept somatomedin, all improving significantly aspect heat stability, anti-trypsin hydrolysis ability, the animal body internal stability, after the aFGF process PEG chemical modification simultaneously, immunogenicity is all reduced largely in its immunoreactivity and the body, so be highly suitable for treating diseases such as burn and scald, fresh wound surface, chronic ulcer, cervical erosion.Because having easy to use, dose, the spray-type medicine is easy to control, be easy to absorb compared with powder or membrane type medicament, and the characteristics that can both be suitable for for the wound surface of the big small size of difference, therefore, in order to promote the use of well with PEG-haFGF PEG-aFGF is the spray of the treatment burns, scalds and chronic ulcer of main medicinal component, demands releasing its spray-type medicine urgently.
Summary of the invention
It is the spray and preparation method thereof of the treatment burns, scalds and chronic ulcer of main medicinal component with PEG-haFGF PEG-aFGF that the object of the invention is to provide a kind of use.
The spray of treatment burns, scalds and chronic ulcer provided by the invention; it is characterized in that its composition by following content forms: the PEG-haFGF of 1-100 μ g/mL, 1-100mg/mL Zedoary turmeric oil, 0.001-0.05mg/mL protective agent, 0.001-0.01mg/mL antiseptic, 0.0001-0.001mg/mL stabilizing agent, 0.01-0.2mg/mL correctives; solvent is normal saline or water for injection, and wherein said protective agent is one or more the mixture in albumin, mannitol, the chitin polysaccharide.
The spray preparing process of treatment burns, scalds and chronic ulcer is made of following steps:
1.: get an amount of PEG-haFGF, protective agent, antiseptic and stabilizing agent and dissolve filtration sterilization then with normal saline or water for injection separately or after mixing;
2.: get an amount of Zedoary turmeric oil and correctives and be dissolved in water for injection or the normal saline, form uniform solution;
3.: with the 1. the mixed solution that obtains of step with the 2. the solution of step acquisition fully mix, make finished product until mixing;
Spray preparing process can also be made of following steps:
1.: get an amount of PEG-haFGF, protective agent, antiseptic and stabilizing agent separately or mix the back with water for injection or physiological saline solution, filter then, degerming;
2.: 1. go on foot gains lyophilization under-50 ℃～-30 ℃ conditions with and make lyophilized powder;
3.: get an amount of Zedoary turmeric oil and correctives and be dissolved in the water for injection;
4.: lyophilized powder is dissolved in normal saline or water for injection, and with the 3. solution mixing that obtain of step, filtration sterilization makes finished product.
Wherein protective agent is a kind of in albumin, mannitol, the chitin polysaccharide or their mixture; Antiseptic is a kind of in sodium benzoate, sorbitol, methyl hydroxybenzoate, ethyl hydroxybenzoate, the butoben or their mixture; Stabilizing agent is EDTA-2Na; Correctives is a kind of in Cortex cinnamomi japonici (Ramulus Cinnamomi) syrup, orange syrup, xylitol, sorbitol, mannitol, apple essence, flavoring banana essence, Folium Stevlae Rebaudianae, red bright alcohol, glycerol, cyclamate, aspartame, fructose, sucralose, Fructus Citri Limoniae, acetic acid lactone potassium, contract two carbonyldioxy amide, agedoite, the acetic acid lactone salt or their mixture, and any apoplexy due to endogenous wind of protective agent, antiseptic, stabilizing agent and correctives a kind of or their mixture can be used with a kind of of other any apoplexy due to endogenous wind or their mixture.
The main medicinal component of spray of the present invention is PEG-aFGF, also contain the Chinese medicine Zedoary turmeric oil in addition, one of temperature Rhizoma Curcumae system " Zhejiang eight flavors ", be traditional genuine medicinal materials, Oleum Curcumae is the volatile oil that warm Rhizoma Curcumae rhizome obtains through distillation, Oleum Curcumae has antiinflammatory, pain relieving, blood circulation promoting and blood stasis dispelling, removing the necrotic tissue and promoting granulation enhancing human body immunity power, antiviral, effect such as anticancer grade, its function cures mainly and is promoting flow of QI and blood, the removing food stagnancy pain relieving, principal indication has: gynecological inflammation, dermatitis, vitiligo, white macula, skin burn, chilblain, rheumatalgia, viral infection is used for the blood stasis amenorrhea, the food stagnation distending pain, early cervical carcinoma.This dosage form has been inherited characteristics such as PEG-aFGF good stability, bioavailability height, non-immunogenicity, having possessed characteristics such as antiinflammatory, antiviral and raising body immunity simultaneously, is the new drug formulation of diseases such as treatment burn and scald, fresh wound surface, chronic ulcer, cervical erosion.
The specific embodiment
Embodiment 1:
(1) gets PEG-haFGF (PEG-aFGF) 1mg, albumin 50mg, ethyl hydroxybenzoate 5mg, EDTA-2Na 0.1mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 1g and Cortex cinnamomi japonici (Ramulus Cinnamomi) syrup 100mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 2:
(1) gets PEG-haFGF (PEG-aFGF) 100mg, mannitol 1mg, sodium benzoate 10mg, EDTA-2Na 0.5mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 20mg and xylitol 10mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 3:
(1) gets PEG-haFGF (PEG-aFGF) 50mg, chitin polysaccharide 30mg, sorbitol 1mg, EDTA-2Na 1mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 100mg and apple essence 200mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 4:
(1) gets PEG-haFGF (PEG-aFGF) 80mg, albumin 10mg, mannitol 5mg, chitin polysaccharide 10mg, methyl hydroxybenzoate 7mg, EDTA-2Na 0.3mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration degerming, and lyophilized powder is made in gains lyophilization under-45 ℃ of conditions; (2) Zedoary turmeric oil 50mg and cyclamate 50mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, filter, degerming; (3) with above-mentioned lyophilized powder and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 5:
(1) gets PEG-haFGF (PEG-aFGF) 60mg, mannitol 20mg, chitin polysaccharide 20mg, sodium benzoate 2mg, sorbitol 4mg, methyl hydroxybenzoate 2mg, EDTA-2Na 0.2mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration degerming, and lyophilized powder is made in gains lyophilization under-45 ℃ of conditions; (2) Zedoary turmeric oil 30mg and acetic acid lactone potassium 80mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, filter, degerming; (3) with above-mentioned lyophilized powder and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 6:
(1) gets PEG-haFGF (PEG-aFGF) 30mg, albumin 20mg, butoben 4.5mg, EDTA-2Na0.6mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration degerming, and lyophilized powder is made in gains lyophilization under-45 ℃ of conditions; (2) Zedoary turmeric oil 60mg and fructose 120mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, filter, degerming; (3) with above-mentioned lyophilized powder and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 7:
(1) gets PEG-haFGF (PEG-aFGF) 75mg, albumin 35mg, ethyl hydroxybenzoate 3mg, EDTA-2Na 0.8mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 40mg and Folium Stevlae Rebaudianae 150mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 8:
(1) gets PEG-haFGF (PEG-aFGF) 55mg, albumin 48mg, ethyl hydroxybenzoate 6mg, EDTA-2Na 0.7mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) the Zedoary turmeric oil 45mg and the two carbonyldioxy amide 180mg that contract are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 9:
(1) gets PEG-haFGF (PEG-aFGF) 40mg, mannitol 5mg, chitin polysaccharide 10mg, ethyl hydroxybenzoate 10mg, EDTA-2Na 0.4mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 75mg and acetic acid lactone salt 130mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 10:
(1) gets PEG-haFGF (PEG-aFGF) 55mg, albumin 48mg, ethyl hydroxybenzoate 6mg, EDTA-2Na 0.7mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 45mg and glycerol 110mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 11:
(1) gets PEG-haFGF (PEG-aFGF) 80mg, albumin 10mg, mannitol 5mg, chitin polysaccharide 10mg, methyl hydroxybenzoate 7mg, EDTA-2Na 0.3mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration degerming, and lyophilized powder is made in gains lyophilization under-45 ℃ of conditions; (2) Zedoary turmeric oil 50mg and orange syrup 50mg, mannitol 50mg, flavoring banana essence 50mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, filter, degerming; (3) with above-mentioned lyophilized powder and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 12:
(1) gets PEG-haFGF (PEG-aFGF) 50mg, chitin polysaccharide 30mg, sorbitol 1mg, EDTA-2Na 1mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 100mg and aspartame 170mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 13:
(1) gets PEG-haFGF (PEG-aFGF) 20mg, albumin 50mg, ethyl hydroxybenzoate 5mg, EDTA-2Na 0.1mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration, degerming; (2) Zedoary turmeric oil 1g and sorbitol 35mg, the pure 100mg of red aquatic foods are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, and filtration sterilization; (3) with above-mentioned PEG-aFGF solution and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Embodiment 14:
(1) gets PEG-haFGF (PEG-aFGF) 60mg, mannitol 20mg, chitin polysaccharide 20mg, sodium benzoate 2mg, sorbitol 4mg, methyl hydroxybenzoate 2mg, EDTA-2Na 0.2mg, with 10mL water for injection or normal saline, preferably physiological saline solution dissolves complete after-filtration degerming, and lyophilized powder is made in gains lyophilization under-45 ℃ of conditions; (2) Zedoary turmeric oil 30mg and sucralose 30mg, Fructus Citri Limoniae 80mg, agedoite 20mg are dissolved in 990mL water for injection or the normal saline, preferably in the water for injection, filter, degerming; (3) with above-mentioned lyophilized powder and the abundant mix homogeneously of Zedoary turmeric oil solution, filtration sterilization, standby.
Below be spray experiment embodiment of the present invention
1, preparation pharmacokinetics characteristics
The employing New Zealand white rabbit is an experimental subject, observe after this invention preparation topical in the intravital pharmacokinetics characteristics of rabbit, evenly be sprayed on any one spray in the above-mentioned example 1 to 6 on the damaged skin model repeatedly during experiment, sprayed slightly do after, with a plastic sheeting parcel medication skin greater than the coating area, to keep moistening, open behind the 6h, and it is centrifugal to get blood in the auricular vein of rabbit, adopt the emitting isotope labelling method to detect blood drug level, analyze pharmacokinetic parameters, the result shows that said preparation has good stability, biological half-life is long, characteristics such as safety is good are compared present acid fibroblast growth factor spray in clinical use, biological half-life improves 5 times nearly, has good market application prospect.
2, repair the effectiveness experiment
The employing miniature pig is an experimental subject, cause miniature pig back rule shape wound surface with the special device of causing injury, during experiment any one spray in the above-mentioned example 1 to 6 is sprayed on the trauma model, change dressings every other day once later on, adopt wound surface to take pictures by different time sections, hyaline membrane is traced weighing method record wound surface area, normal dyeing after formalin fixed, the growth of primary part observation wound surface granulation tissue (comprises the blood capillary growth, collagen deposition) changes with re-epithelialization, the result shows, this invention spray can promote the growth of wound surface granulation tissue, induce the blood capillary plumule to form and re-epithelialization, wound repair is had obvious facilitation.
3, antibacterial efficacy experiment
Getting cultured staphylococcus aureus bacterium liquid 200uL evenly coats on the solid SCDLP flat board.Gently place sterilized little filter paper on the flat board with aseptic nipper, drip respectively on filter paper with any one spray in the above-mentioned example 1 to 6 of 10uL then, after treating that sample permeates fully, place 37 ℃ of incubators to cultivate 6-8 hour on culture dish, take out culture dish, observe the inhibition zone size.The result shows the inhibition zone of all visible diameter 8-10mm of above-mentioned observation sample, and the content of what and readability and Zedoary turmeric oil of inhibition zone has good dependency.
Claims (6)
1, a kind of spray for the treatment of burns, scalds and chronic ulcer; it is characterized in that its composition by following content forms: the PEG-haFGF of 1-100 μ g/mL, 1-100mg/mL Zedoary turmeric oil, 0.001-0.05mg/mL protective agent, 0.001-0.01mg/mL antiseptic, 0.0001-0.001mg/mL stabilizing agent, 0.01-0.2mg/mL correctives; solvent is normal saline or water for injection, and wherein said protective agent is one or more the mixture in albumin, mannitol, the chitin polysaccharide.
2, the spray of treatment burns, scalds and chronic ulcer according to claim 1 is characterized in that: described antiseptic is one or more the mixture in sodium benzoate, sorbitol, methyl hydroxybenzoate, ethyl hydroxybenzoate, the butoben.
3, the spray of treatment burns, scalds and chronic ulcer according to claim 1 is characterized in that: stabilizing agent is EDTA-2Na.
4, the spray of treatment burns, scalds and chronic ulcer according to claim 1 is characterized in that: described correctives is one or more the mixture in Cortex cinnamomi japonici (Ramulus Cinnamomi) syrup, orange syrup, xylitol, sorbitol, mannitol, apple essence, flavoring banana essence, Folium Stevlae Rebaudianae, red bright alcohol, glycerol, cyclamate, aspartame, fructose, sucralose, Fructus Citri Limoniae, acetic acid lactone potassium, contract two carbonyldioxy amide, agedoite, the acetic acid lactone salt.
5, a kind of spray preparing process of treatment burns, scalds and chronic ulcer according to claim 1 is characterized in that being made of following steps:
1.: get an amount of PEG-haFGF, protective agent, antiseptic and stabilizing agent and dissolve filtration sterilization then with normal saline or water for injection separately or after mixing;
2.: get an amount of Zedoary turmeric oil and correctives and be dissolved in water for injection or the normal saline, form uniform solution;
3.: with the 1. the mixed solution that obtains of step with the 2. the solution of step acquisition fully mix, make finished product until mixing.
6, a kind of spray preparing process of treatment burns, scalds and chronic ulcer according to claim 1 is characterized in that being made of following steps:
1.: get an amount of PEG-haFGF, protective agent, antiseptic and stabilizing agent separately or mix the back with water for injection or physiological saline solution, filter then, degerming;
2.: 1. go on foot gains lyophilization under-50 ℃～-30 ℃ conditions with and make lyophilized powder;
3.: get an amount of Zedoary turmeric oil and correctives and be dissolved in the water for injection;
4.: lyophilized powder is dissolved in normal saline or water for injection, and with the 3. solution mixing that obtain of step, filtration sterilization makes finished product.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005100942032A CN100548370C (en) | 2005-08-30 | 2005-08-30 | A kind of spray for the treatment of burns, scalds and chronic ulcer and preparation method thereof |
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| CNB2005100942032A CN100548370C (en) | 2005-08-30 | 2005-08-30 | A kind of spray for the treatment of burns, scalds and chronic ulcer and preparation method thereof |
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| CN1739775A CN1739775A (en) | 2006-03-01 |
| CN100548370C true CN100548370C (en) | 2009-10-14 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102363019B (en) * | 2007-07-27 | 2013-03-20 | 烟台大学 | Curcuma zedoary oil extract, preparation method thereof and purpose thereof |
| CN114887037B (en) * | 2022-03-31 | 2024-03-15 | 温州医科大学 | Biphasic spray for treating diabetic foot ulcers |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1485091A (en) * | 2002-09-23 | 2004-03-31 | 武汉格瑞生物工程有限公司 | Biopreparate for healing wounded surface and curing intractable ulcer |
| CN1583090A (en) * | 2004-06-08 | 2005-02-23 | 广州暨南大学医药生物技术研究开发中心 | Spray agent of aromatic turmeric rlizome oil and its preparation |
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2005
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1485091A (en) * | 2002-09-23 | 2004-03-31 | 武汉格瑞生物工程有限公司 | Biopreparate for healing wounded surface and curing intractable ulcer |
| CN1583090A (en) * | 2004-06-08 | 2005-02-23 | 广州暨南大学医药生物技术研究开发中心 | Spray agent of aromatic turmeric rlizome oil and its preparation |
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| Title |
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| aFGF对大鼠胃粘膜溃疡的促愈合作用. 孙黎光等.中国医科大学学报，第31卷第1期. 2002 |
| aFGF对大鼠胃粘膜溃疡的促愈合作用. 孙黎光等.中国医科大学学报，第31卷第1期. 2002 * |
| 人酸性成纤维细胞生长因子突变体表达与修饰. 郑青等.华南理工大学学报自然科学版，第23卷第1期. 2005 |
| 人酸性成纤维细胞生长因子突变体表达与修饰. 郑青等.华南理工大学学报自然科学版，第23卷第1期. 2005 * |
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| 重组人酸性成纤维细胞生长因子促进大鼠烫伤愈合的研究. 许华等.暨南大学学报（医学版），第24卷第2期. 2003 * |
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Inventor after: Li Xiaokun Inventor after: Huang Zhifeng Inventor after: Wang Xiaojie Inventor after: Tian Haishan Inventor after: Xiao Jian Inventor after: Feng Zhiguo Inventor after: Tang Lu Inventor after: Hui Qi Inventor after: Zhang Yi Inventor before: Li Xiaokun Inventor before: Huang Zhifeng Inventor before: Xiao Jian Inventor before: Ni Chunyan Inventor before: Zhang Yi |
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Free format text: CORRECT: INVENTOR; FROM: LI XIAOKUN HUANG ZHIFENG XIAO JIAN NI CHUNYAN ZHANG YI TO: LI XIAOKUN HUANG ZHIFENG WANG XIAOJIE TIAN HAISHAN XIAO JIAN FENG ZHIGUO TANG LU HUI QI ZHANG YI |
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