CN114129710A - Fibroblast growth factor hydrogel and preparation method thereof - Google Patents
Fibroblast growth factor hydrogel and preparation method thereof Download PDFInfo
- Publication number
- CN114129710A CN114129710A CN202111497873.4A CN202111497873A CN114129710A CN 114129710 A CN114129710 A CN 114129710A CN 202111497873 A CN202111497873 A CN 202111497873A CN 114129710 A CN114129710 A CN 114129710A
- Authority
- CN
- China
- Prior art keywords
- hydrogel
- growth factor
- fibroblast growth
- bfgf
- carbomer
- 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.)
- Granted
Links
- 102000018233 Fibroblast Growth Factor Human genes 0.000 title claims abstract description 35
- 108050007372 Fibroblast Growth Factor Proteins 0.000 title claims abstract description 35
- 229940126864 fibroblast growth factor Drugs 0.000 title claims abstract description 34
- 239000000017 hydrogel Substances 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims abstract description 37
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 claims abstract description 12
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 10
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 10
- 230000001154 acute effect Effects 0.000 claims abstract description 10
- 229960001631 carbomer Drugs 0.000 claims abstract description 10
- 239000008367 deionised water Substances 0.000 claims abstract description 10
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 10
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 10
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 208000030886 Traumatic Brain injury Diseases 0.000 claims abstract description 9
- 230000009529 traumatic brain injury Effects 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims abstract 5
- 108010025899 gelatin film Proteins 0.000 claims description 8
- 229960001570 ademetionine Drugs 0.000 claims description 7
- 230000008439 repair process Effects 0.000 claims description 7
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 239000006185 dispersion Substances 0.000 claims description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- 206010052428 Wound Diseases 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 208000029028 brain injury Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 19
- 239000000499 gel Substances 0.000 abstract description 18
- 239000003814 drug Substances 0.000 abstract description 16
- 238000005516 engineering process Methods 0.000 abstract description 4
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 32
- 230000000052 comparative effect Effects 0.000 description 9
- 210000005036 nerve Anatomy 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 5
- 239000002243 precursor Substances 0.000 description 4
- 239000008279 sol Substances 0.000 description 4
- 208000028389 Nerve injury Diseases 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000008764 nerve damage Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 208000020154 Acnes Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000004221 Multiple Trauma Diseases 0.000 description 1
- 208000023637 Multiple injury Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- 206010048245 Yellow skin Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000023105 myelination Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 description 1
- 229960001227 oxiracetam Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
Abstract
The invention relates to a fibroblast growth factor hydrogel and a preparation method thereof, wherein the hydrogel comprises 0.1-0.3 wt% of fibroblast growth factor (bFGF), 3-6 wt% of carbomer, 2-4 wt% of hyaluronic acid, 4-8 wt% of adenosylmethionine, a proper amount of pH regulator and the balance of deionized water. The invention improves the stability of the medicament to a certain extent, enhances the directional effect of the medicament application, exerts the plasticity and the use adaptability of the gel to a certain extent and provides a new scheme for treating acute traumatic brain injury by adopting a physical mixing technology of bFGF and carmowu, hyaluronic acid and adenosylmethionine in a specific ratio.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a fibroblast growth factor hydrogel and a preparation method thereof.
Background
With the continuous improvement of the economic level of modern society, the rapid development of high-speed traffic networks, and the active expansion of industries such as the construction industry, acute Traumatic Brain Injury (TBI) has gradually become an important problem threatening human health in the fields of clinical first aid and critical medicine. In developed countries dominated by europe and the united states, approximately 260 million people per year are covered in the shadow of acute traumatic brain injury, and in these patients, over 40% remain permanently disabled. As one of the main diseases accompanied by multiple injuries, the incidence rate of acute traumatic brain injury in China is increased sharply in recent years, and the mortality rate is between 2.7 and 21.8 percent. The high fatality rate and disability rate of the traditional Chinese medicine become main medical problems in the medical field and even the whole society.
At present, the clinical commonly used treatment means are acute-phase operation and convalescent-phase neurotrophic medicaments, the operation only takes life saving as the first aim, and the effects of the commonly used medicaments such as brain protein extract, oxiracetam and the like are not exact. For the key factors influencing prognosis and quality of life, such as recovery of nerve function, protection of blood brain barrier and improvement aiming at myelination of neurons, higher limitation exists, and no specific medicine exists clinically up to now. Therefore, the search for a candidate drug for improving nerve function and promoting nerve repair in the acute phase after acute traumatic brain injury has been a hot and key problem for the research and development of new drugs in the field for a long time. Growth factor-type drugs have long been considered to have good potential in treating nerve injury and promoting recovery of nerve function. A plurality of Fibroblast Growth Factor (FGF) products, such as Beifuji, Beifuxin and Chuangbi, which are independently developed by research teams of the applicant are applied to clinic, and proved for more than twenty years, the products show good safety and effectiveness, but are mainly used for wound repair, such as the fields of skin, corneal ulcer, refractory chronic wounds and the like. In the field of nerve injury and repair, Basic fibroblast growth factor (bFGF) and a signal path mediated by the bFGF are found to play an important role in the processes of nerve function recovery, blood brain barrier repair and the like after acute central nerve trauma according to the previous research results. However, because the protein activity is unstable, the degradation and inactivation are easy, the half-life period is short, and the like, the clinical application is limited, so that the development of a gel preparation for open nerve injury is hoped, the activity and stability of the drug protein are protected, the drug action time is prolonged, the gel preparation is better suitable for a defective focus, and the drug can play a role in promoting nerve repair at an injury part in the early stage of injury.
Chinese patent application CN113069533A discloses a long-acting fibroblast growth factor gel, which belongs to the field of fibroblast growth factors and solves the problem of poor effect of intramuscular injection of bFGF related drugs in the prior art, and the technical scheme for solving the problem is mainly that the long-acting fibroblast growth factor gel is formed by mixing polyethylene glycol diacrylate and rhbFGF stock solution with the purity of more than 99 percent, the concentration of the long-acting fibroblast growth factor gel is 500000 IU/mL-550000 IU/mL, and the viscosity of the long-acting fibroblast growth factor gel is 45-55 Pa.s. The application is mainly used for directly acting the long-acting fibroblast growth factor gel on the optic nerve fibers, and has the advantages of slow absorption, good biocompatibility, realization of slow release of the medicine and better treatment effect.
Chinese patent application CN108721136A discloses a repair gel and a preparation method and application thereof, relating to the technical field of skin care products, wherein the skin care gel comprises basic fibroblast growth factor bFGF and precursor sol; the mass ratio of the basic fibroblast growth factor bFGF to the precursor sol is 1-2: 1000000. the bFGF can keep better stability in the precursor sol, still has better activity after being stored for half a year at the normal temperature through detection, and effectively solves the problem that the existing skin care product containing the bFGF component is not well stored at the normal temperature. Meanwhile, the components in the precursor sol and the bFGF are matched for use, so that the original effects can be exerted respectively, the components can play a synergistic effect, the curative effect is further enhanced, and the skin care product is obviously better than the existing skin care products in relieving symptoms such as dry skin, aging, dark yellow skin, color spots, acnes, allergy and the like.
Although the prior art has disclosed bFGF gels, it would be desirable to be able to find a suitable carrier: the price is low and the raw materials are easy to obtain; has excellent biocompatibility; can be degraded by itself; can slowly and stably release bFGF, and prolongs the action time of bFGF.
Disclosure of Invention
Based on the above background art, the technical problem to be solved by the present invention is to provide a fibroblast growth factor hydrogel and a preparation method thereof, which can maintain the activity of fibroblast growth factor at room temperature and rapidly release active ingredients at elevated temperature (for example, when reaching normal body temperature). In order to realize the purpose of the invention, the following technical scheme is adopted:
the invention relates to a fibroblast growth factor hydrogel, which comprises 0.1-0.3 wt% of fibroblast growth factor (bFGF), 3-6 wt% of carbomer, 2-4 wt% of hyaluronic acid, 4-8 wt% of adenosylmethionine, a proper amount of pH regulator and the balance of deionized water.
In a preferred embodiment of the invention, the hydrogel is a film. The hydrogel is arranged into a film form, so that the hydrogel can be directly used as a dressing for a wound part of brain injury.
In a preferred embodiment of the present invention, the hydrogel has a pH of 6.5 to 7.5.
In a preferred embodiment of the invention, the amount of ademetionine is from 6 to 8% by weight. The present invention contributes to further improving the storage stability of fibroblast growth factor (bFGF) by the preferred amount of ademetionine.
In a preferred embodiment of the invention, the carbomer is selected from the group consisting of carbomer 941 and/or carbomer 942; carbomer 941 is preferred.
In a preferred embodiment of the present invention, the fibroblast growth factor hydrogel has a significantly changed release rate of fibroblast growth factor (bFGF) at 37.0 ℃.
The invention also relates to a preparation method of the fibroblast growth factor hydrogel, which comprises the following steps:
1. adding deionized water into a preparation tank, adding hyaluronic acid and methionine, heating to 50-70 ℃, and uniformly stirring for later use;
2. dissolving carbomer in the rest deionized water heated to 80-95 deg.C, cooling to room temperature, adding fibroblast growth factor (bFGF), and stirring;
3. and (3) mixing the dispersions obtained in the step (1) and the step (2), adjusting the pH, placing the mixture into a container with a plane bottom surface, and cooling at room temperature to obtain a gel film.
The invention also relates to application of the hydrogel, which is applied to rapid repair of acute traumatic brain injury.
Advantageous effects
The invention improves the stability of the medicament to a certain extent, enhances the directional effect of the medicament application, exerts the plasticity and the use adaptability of the gel to a certain extent and provides a new scheme for treating acute traumatic brain injury by adopting a physical mixing technology of bFGF and carmowu, hyaluronic acid and adenosylmethionine in a specific ratio.
Drawings
FIG. 1: the release rate of fibroblast growth factor at different temperatures.
Detailed Description
In order to further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless otherwise specified, the reagents involved in the examples of the present invention are all commercially available products, and all of them are commercially available.
Example 1: a preparation method of fibroblast growth factor hydrogel comprises the following steps:
the preparation method comprises the following steps:
1. adding deionized water of which the total amount is half of the total amount in a preparation tank, adding hyaluronic acid and methionine, heating to 60 ℃, and uniformly stirring for later use;
2. dissolving carbomer 941 in the rest deionized water heated to 90 ℃, cooling to room temperature, adding fibroblast growth factor (bFGF), and stirring uniformly for later use;
3. mixing the dispersion obtained in step 1 and step 2, adjusting pH to 7.0, placing in a culture dish, and standing at room temperature to obtain a gel film with a thickness of 2 mm.
Example 2: a preparation method of fibroblast growth factor hydrogel comprises the following steps:
a gel film having a thickness of 2mm was obtained in the same manner as in example 1.
Example 3: a preparation method of fibroblast growth factor hydrogel comprises the following steps:
a gel film having a thickness of 2mm was obtained in the same manner as in example 1.
Comparative example 1:
same as example 1, except that S-adenosylmethionine was not added.
Comparative example 2:
same as example 1, except that hyaluronic acid was not added.
Comparative example 3:
the same as example 1 except that without adding carbomer 941, fibroblast growth factor (bFGF) was directly dissolved in deionized water in step (2).
Example 4: stability evaluation test
The activity of the basic fibroblast growth factor in the newly prepared samples, stored at 4 ℃ for 2 months and stored at 25 ℃ for 2 months is respectively determined, and the specific experimental steps are as follows:
(1) the gel films to be tested are respectively taken, cut into the size of 2cm multiplied by 2cm, and placed in 4mL PBS buffer solution with the pH value of 7.4, the PBS buffer solution is kept at 37 ℃, and the gel films are released for 2 hours by shaking.
(2) Adding the PBS buffer solution obtained in the step (1) into micropores of an enzyme detection plate to perform ELISA content determination (refer to the technology of frugal, xu Xiao Peng, Wang hong, and the like. basic fibroblast growth factor monoclonal antibody ELISA microscale detection, the technology of journal of Chinese immunology, 2006, 22(4)), determining the optical density of bFGF at 450nm, and repeating the determination for 3 times.
(3) For ease of comparison, the assay results for each freshly prepared sample were normalized to 100%, and the activity of the stored sample was taken as its activity data as a percentage of the assay result relative to the results of the corresponding freshly prepared sample for that sample, and the experimental results are shown in table 1.
Table 1 stability evaluation test results
Group of | Novel preparation | Storing at 4 deg.C for 2 months | Storing at 25 deg.C for 2 months |
Example 1 | 100±5% | 92±6% | 82±7% |
Example 2 | 100±7% | 87±5% | 76±8% |
Example 3 | 100±6% | 85±7% | 74±6% |
Comparative example 1 | 100±5% | 42±4% | 31±3% |
Comparative example 2 | 100±7% | 57±8% | 45±5% |
Comparative example 3 | 100±8% | 62±7% | 48±6% |
As can be seen from the above, when stored at both room temperature (25 ℃ C.) and 4 ℃ C, bFGF activity decreases in order with the storage time; the low temperature is beneficial to maintaining the bFGF activity, the loss of the bFGF activity is relatively quick when the bFGF is stored at the normal temperature, but the bFGF activity loss can be obviously reduced in the embodiment of the invention, and particularly, the formula in the embodiment 1 has the highest stability. In contrast, comparative example 1, which lacks S-adenosylmethionine, showed the most significant decrease in activity, which indicates that S-adenosylmethionine, carbomer and hyaluronic acid in a specific ratio is helpful for improving the long-term storage stability of fibroblast growth factor hydrogel.
Example 5: evaluation test of Release efficiency
The prepared gel films are respectively taken to be 2cm multiplied by 2cm and placed in PBS buffer solution with the pH value of 4ml and 7.4, and the gel films are completely immersed in the PBS solution. The temperature of PBS was controlled, respectively, the concentration of fibroblast growth factor (bFGF) in the PBS buffer solution was measured after 1 hour of immersion and the amount of fibroblast growth factor (bFGF) released from the gel film was estimated. The amount of released fibroblast growth factor (bFGF) of the gel film at different temperatures for 1 hour was determined based on the amount of original bFGF and the amount of released bFGF in the gel film.
Referring to fig. 1, it can be seen from fig. 1 that the gel films of examples 1 to 3 show a significant change in release rate at 37.5 ℃, thereby illustrating that the gel films of examples have temperature sensitivity around 37.5 ℃. Unlike the examples, comparative examples 1-3 showed less pronounced tendency of the release rate to change with temperature, and particularly comparative example 1, which lacks temperature sensitivity due to the absence of S-adenosylmethionine, although the release rate was higher.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.
Claims (8)
1. A fibroblast growth factor hydrogel comprises 0.1-0.3 wt% of fibroblast growth factor bFGF, 3-6 wt% of carbomer, 2-4 wt% of hyaluronic acid, 4-8 wt% of adenosylmethionine, a proper amount of pH regulator and the balance of deionized water.
2. The hydrogel according to claim 1, which is a film, and the hydrogel is provided in the form of a film, so that the hydrogel can be directly used as a dressing for a wound part of brain injury.
3. The hydrogel according to claim 1, wherein the hydrogel has a pH of 6.5 to 7.5.
4. The hydrogel of claim 1, wherein said ademetionine is present in an amount of 6-8 wt%.
5. The hydrogel of claim 1, said carbomer being selected from the group consisting of carbomer 941 and/or carbomer 942; carbomer 941 is preferred.
6. The hydrogel of claim 1, wherein the fibroblast growth factor hydrogel has a significant change in the rate of release of fibroblast growth factor (bFGF) at 37.0 ℃.
7. A process for the preparation of a hydrogel according to any one of claims 1 to 6, which process comprises the following steps:
(1) adding deionized water into a preparation tank, adding hyaluronic acid and methionine, heating to 50-70 ℃, and uniformly stirring for later use;
(2) dissolving carbomer in the rest deionized water heated to 80-95 deg.C, cooling to room temperature, adding fibroblast growth factor bFGF, and stirring;
(3) and (3) mixing the dispersion obtained in the step (1) and the dispersion obtained in the step (2), adjusting the pH, placing the mixture in a container with a plane bottom surface, and cooling at room temperature to obtain a gel film.
8. Use of the hydrogel of any one of claims 1 to 6 for the rapid repair of acute traumatic brain injury.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111497873.4A CN114129710B (en) | 2021-12-09 | Fibroblast growth factor hydrogel and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111497873.4A CN114129710B (en) | 2021-12-09 | Fibroblast growth factor hydrogel and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114129710A true CN114129710A (en) | 2022-03-04 |
CN114129710B CN114129710B (en) | 2024-04-26 |
Family
ID=
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1733294A (en) * | 2005-08-10 | 2006-02-15 | 南海朗肽制药有限公司 | Recombined human alkaline fibroblast growth factor gelling agent and process for preparing the same |
CN1814279A (en) * | 2005-01-31 | 2006-08-09 | 北京双鹭立生医药科技有限公司 | Regenerated human alkali fiber-cell growth factor gel former and preparing method |
US20080226724A1 (en) * | 2007-01-19 | 2008-09-18 | Genentech, Inc. | Prevention of hydrogel viscosity loss |
CN102695514A (en) * | 2009-07-28 | 2012-09-26 | Msi甲基化物科学公司 | S-adenosylmethionine formulations with enhanced bioavailability |
CN105816911A (en) * | 2016-05-31 | 2016-08-03 | 武汉兵兵药业有限公司 | Repairing gel containing growth factors and preparation method of repairing gel |
WO2019066505A1 (en) * | 2017-09-29 | 2019-04-04 | 주식회사 엘지화학 | Composition for pharmaceutical stabilization of hyaluronic acid-based hydrogel and preparing method therefor |
CN111630154A (en) * | 2017-12-20 | 2020-09-04 | 菲格内有限责任公司 | Enhancing fibroblast regenerative activity |
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1814279A (en) * | 2005-01-31 | 2006-08-09 | 北京双鹭立生医药科技有限公司 | Regenerated human alkali fiber-cell growth factor gel former and preparing method |
CN1733294A (en) * | 2005-08-10 | 2006-02-15 | 南海朗肽制药有限公司 | Recombined human alkaline fibroblast growth factor gelling agent and process for preparing the same |
US20080226724A1 (en) * | 2007-01-19 | 2008-09-18 | Genentech, Inc. | Prevention of hydrogel viscosity loss |
CN102695514A (en) * | 2009-07-28 | 2012-09-26 | Msi甲基化物科学公司 | S-adenosylmethionine formulations with enhanced bioavailability |
CN105816911A (en) * | 2016-05-31 | 2016-08-03 | 武汉兵兵药业有限公司 | Repairing gel containing growth factors and preparation method of repairing gel |
WO2019066505A1 (en) * | 2017-09-29 | 2019-04-04 | 주식회사 엘지화학 | Composition for pharmaceutical stabilization of hyaluronic acid-based hydrogel and preparing method therefor |
CN111630154A (en) * | 2017-12-20 | 2020-09-04 | 菲格内有限责任公司 | Enhancing fibroblast regenerative activity |
US20210180020A1 (en) * | 2017-12-20 | 2021-06-17 | Figene, Llc | Augmentation of fibroblast regenerative activity |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6653284B2 (en) | Keratinocyte growth factor-2 formulations | |
Koob et al. | Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing | |
JP2988925B2 (en) | Medical products comprising stable compositions of biologically active polypeptides | |
Namazi et al. | Strategies for prevention of scars: what can we learn from fetal skin? | |
Adzick et al. | Scarless fetal healing. Therapeutic implications. | |
US5589451A (en) | Methods and treaments for corneal healing with hepatocyte and keratinocyte growth factors | |
US20140235539A1 (en) | Composite Collagen Sponge and Preparation Method Thereof | |
JPH07504650A (en) | Inhibition of transforming growth factor β to prevent extracellular matrix accumulation | |
JP2003512433A (en) | Use of GDNF to treat corneal defects | |
CN101143212A (en) | Recombination human acidic mechanocyte growth factor temperature sensitive type gel preparation and preparation method thereof | |
JP3236916B2 (en) | Drugs having cell and tissue regenerating activity, stabilized compositions containing the drugs and their therapeutic, surgical and cosmetic uses | |
JP2003500456A (en) | Keratinocyte growth factor-2 preparation | |
Wang et al. | Characterization, stability, and formulations of basic fibroblast growth factor | |
Bensaid et al. | Autocrine regulation of bovine retinal capillary endothelial cell (BREC) proliferation by BREC-derived basic fibroblast growth factor | |
Yao et al. | MiR-182 inhibits oxidative stress and epithelial cell apoptosis in lens of cataract rats through PI3K/Akt signaling pathway. | |
CN114129710A (en) | Fibroblast growth factor hydrogel and preparation method thereof | |
D'Amore | Heparin-endothelial cell interactions | |
CN109793913A (en) | Sustained release film dressing comprising epidermal growth factor | |
US20230172994A1 (en) | Methods of promoting vasculogenesis | |
Wu et al. | Retracted: Effects of gene knockdown of CNP on ventricular remodeling after myocardial ischemia‐reperfusion injury through NPRB/Cgmp signaling pathway in rats | |
CN114129710B (en) | Fibroblast growth factor hydrogel and preparation method thereof | |
CN102357243B (en) | Recombinant cattle basic fibroblastic growth factor eye drops | |
JP4832515B2 (en) | Wound healing composition and use thereof | |
CN102861320B (en) | Spray for treating skin and mucosa wounds | |
Assani et al. | M1 to M2 induction in macrophages using a retinoic acid-releasing mesenchymal stem cell scaffold |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant |