CN108815563A - A kind of gelatin hemostatic material and its preparation process - Google Patents
A kind of gelatin hemostatic material and its preparation process Download PDFInfo
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- CN108815563A CN108815563A CN201810813845.0A CN201810813845A CN108815563A CN 108815563 A CN108815563 A CN 108815563A CN 201810813845 A CN201810813845 A CN 201810813845A CN 108815563 A CN108815563 A CN 108815563A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/104—Gelatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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Abstract
The invention discloses a kind of gelatin hemostatic materials and its preparation process, preparation process to include the following steps：(1) gelatine starting material carries out pre-treatment；(2) match ash, pre- liming, chopping, liming, move back ash；(3) it neutralizes, wash, endure glue；(4) gelatin hemostatic material is prepared；(5) dress, sterilizing, outer packing is wrapped inside in gelatin hemostatic material.It supplies disposable gelatin hemostatic material with germ-free condition, which has good physicochemical property and biology performance, can be degraded and absorbed, advantageously promote wound healing, is suitable for capillary, vein and artery hemostasis and diffusivity bleeding.
Description
Technical field
The present invention relates to a kind of hemostatic material and its preparation processes, belong to pharmaceutical technology field, in particular to one kind has
The gelatin hemostatic material and its preparation process of excellent biocompatibility.
Background technique
In the world many developed countries at present all in research, exploitation, utilize gelatin.Especially grinding to its medical value
Study carefully, develop, using attaching the importance, wherein being maintained the leading position with the U.S..Many scientific research departments of China are also energetically by gelatin
For in daily life.
Gelatin is different according to raw materials for production, production method and product quality, product purpose, is divided into edible gelatin, medicinal bright
Glue, industrial gelatine, photographic gelatin and hide glue, gelatine.It is mainly used in edible gelatin, biomembrane material, medical fibre, group
Knit reparation and substitution, industrial gelatine.
The production method of existing gelatin mainly has milk of lime process and hydrochloric acid method, and how to provide one kind simply can be mass-produced
Gelatin and the preparation process that gelatin hemostatic material is made are those skilled in the art's technical problems urgently to be solved.
Summary of the invention
For overcome the deficiencies in the prior art, it is an object of the present invention to provide a kind of gelatin hemostatic material and its preparation processes.
The product is to be suitable for germ-free condition supply and disposable gelatin hemostatic material to capillary, vein and artery
Hemostasis and diffusivity bleeding.
In order to achieve the above object, the present invention uses following technical scheme：
The present invention provides a kind of preparation process of gelatin hemostatic material, includes the following steps：
(1) gelatine starting material carries out pre-treatment；
(2) match ash, pre- liming, chopping, liming, move back ash；
(3) it neutralizes, wash, endure glue；
(4) gelatin hemostatic material is prepared；
(5) dress, sterilizing, outer packing is wrapped inside in gelatin hemostatic material.
Further, in step (1), the pre-treatment is：The cladding of variety classes, different parts is separately handled, is cut
At the strip of 10cm wide；The cladding be selected from dry hide or fresh hide, ox-hide or pigskin, cattle hide or buffalo hide, upper splitting or under cut open
One of skin, scalp, foot skin are a variety of.
Further, described to be with ash in step (2)：Quick lime is first added water be made into thick slurry, 1 kilogram of lime adds water
It 1.2-1.5 kilograms, stores 12-18 days or so, is diluted with water, filters out coarse granule, it is spare；The pre- liming is：With containing about 1%
The limewash of calcium oxide impregnates cladding 2-3 days.
Further, in step (2), the chopping is：Cladding is cut into less than 10cm3Block, cut size should phase
Closely.
Further, in step (2), the liming is：Cladding is impregnated with limewash；When liming, limewash internal oxidition calcium
Content is controlled in 2-4%；The ash that moves back is：Under constant stirring, it is primary to change within every 30 minutes water, total 10-15 times or so；It is later every
It is primary to change water within 1 hour；The ratio of raw material and water should be 1: 6 or so every time；It completes within 24-36 hours to move back ash, pH is 9.5 or so.
Further, in step (3), the neutralization is：First plus water keeps cladding submerged in water, starts stirring, will be dilute
The hydrochloric acid solution for releasing one times or more water is slowly added into water, and keeping pH is 3 or so, and when neutralizing beginning, every 30 minutes acid addings are primary,
After 4 hours, every 1 hour acid adding is primary, adds all acid within about 8 hours, continues stirring 4-8 hours.
Further, in step (3), the washing is：It keeps stirring, it is primary to change within every 1 hour water, changes altogether 10 times or so；
The pH value of skin should meet 5.5 or so after washing.
Further, in step (3), the glue of enduring is：A certain amount of water is first put to glue pot, is heated to enduring glue lowest temperature
55 DEG C of degree, then pours into glue pot for the cladding washed, adding water submerges cladding just, is to slowly warm up to endure glue temperature
65-100 DEG C, pH should be controlled 5.5 or so.
Further, in step (4), it is described prepare gelatin hemostatic material the specific steps are：It is equal that gelatin is subjected to ultrasonic wave
Matter, the methods of the assembly after homogeneous is boiled, is suspended, is spraying is made small porous particle to get gelatin hemostatic material.
Preferably, in step (4), the boiling is that it is made to generate boiling effect in the case where negative pressure with the method for vacuum
Water for injection is atomized by fruit, is sprayed on the gelatin of boiling, and the little particle of gelatin is made to be bonded to particle through spraying water, passes through tune
Droplet size is saved to control gelatin corpuscle partial size, porous gelatin corpuscle can be obtained through drying.
Preferably, in step (4), the suspension is that gelatin is mixed into lotion with water for injection in proportion, by the lotion
It is sprayed into spraying method in 50 DEG C -80 DEG C of closed bin, and suitably enters the lotion that negative pressure is sparged into and suspend and dry.
The present invention provides a kind of gelatin hemostatic material, is made by preparation process as described above.
Compared with prior art, the invention has the advantages that：
(1) present invention is with germ-free condition supply and disposable gelatin hemostatic material, the product can be degraded and absorbed,
Histologic reaction is good, can advantageously promote wound healing；
(2) product gelatin hemostatic material of the invention has good physicochemical property and biology performance, does not discharge and takes the post as
What generates the substance of side effect to patient, has good biocompatibility, and inside and outside safety experiment has no toxic side effect；Through trying
It tests, is valid up to 2 years；
(3) product gelatin hemostatic material of the invention is suitable for capillary, vein and artery hemostasis and diffusivity
Bleeding can be widely used in various wounds and the hemostasis of all kinds of surgical wound surfaces.
Detailed description of the invention
(a) and (b) of Fig. 1 is respectively gelatin hemostatic material scanning electron microscope sectional view and plan view in effect experimental examples 2.
Specific embodiment
Now in conjunction with attached drawing, the invention will be further described with specific embodiment.
With germ-free condition supply and disposable absorbability gelatin hemostatic material, which is suitable for pair the present invention
Capillary, vein and artery hemostasis and diffusivity bleeding, can be widely used in various wounds and all kinds of surgical wound surfaces stop
Blood.
Absorbability gelatin hemostatic material is that one kind is applied to the bleeding surface of a wound, the medical material with hemostasia effect.
Product after being packaged sterilizing should be stored in relative humidity no more than 65%, non-corrosive gas, cool place, drying,
Draughty interior.
Embodiment 1
1.1 raw material
Cladding：Dry hide or fresh hide, ox-hide or pigskin, cattle hide or buffalo hide, upper splitting or lower splitting, scalp, foot skin.
Different types of cladding will separate, and the skin of different parts will also be separated and be handled.
It deoils：Chuck Steak on fresh pig skin, is scraped off with knife.
Live pig skin first uses 5% dense limewash or 0.5~1% sodium sulfide solution to impregnate, and hair is removed.
The skin of bulk is cut into the strip of 10cm wide.
1.2 with ash
Quick lime first adds water to be made into thick slurry, and 1 kilogram of lime adds 1.2-1.5 kilograms of water, stores 15 days or so, is diluted with water,
Coarse granule is filtered out, it is spare.
With ash with carrying out in ashpit, by required concentration Jia Shui and thick slurry, under constant stirring, with slush pump by limewash
Squeeze into preimpregnation ashpit.
1.3 pre- limings
The effect of pre- liming is to make tentatively to expand, except blood stains, foul and the stink in peeling；Make additionally, due to skin and lime
With making skin become stiffening, it is easier to cut off when cutting skin.
Pre- liming carries out in pre- soaking pit, is impregnated cladding 2 days with the limewash containing about 1% calcium oxide.
1.4 chopping
The purpose of chopping is to speed up liming and endures the speed of glue.
Cladding is cut into less than 10cm with dermatome3Block.
Cut size should be close, keep liming effect consistent.
1.5 liming
Cladding is impregnated with limewash.
When liming, limewash internal oxidition calcium content is controlled at 2-4% (specific gravity 1.015-1.035).Using low when temperature is high
Concentration uses high concentration when temperature is low.
Lime water is 4 times of wet skin when liming, and pH control is controlled in 12-12.5, temperature at 10 DEG C or so, and highest cannot
More than 20 DEG C.
After liming reaches terminal, limewash is bled off.
1.6 move back ash
The purpose for moving back ash is the lime and other sundries (such as solubilising protein) for removing cladding absorption.
Ash is moved back to carry out in neutralization pond, under constant stirring, it is primary to change within every 30 minutes water, and totally 10 times or so.Every 1 is small later
Shi Huanshui is primary.The ratio of raw material and water should be 1: 6 or so every time, and general 24 hours achievable to move back ash.
It whether thorough moves back ash, with phenolphthalein test solution inspection, takes one piece of skin, a few drop phenolphthalein indicators are dripped above skin, when in light
When red (pH is 9.5 or so), i.e., explanation, which moves back ash, to terminate, and otherwise need to continue to move back ash.
1.7 neutralizing
Neutralize the calcium salt made a return journey with acid and allowance for bark that middle collagen and calcium oxide combine.
First plus water keeps cladding submerged in water, starts stirring, the hydrochloric acid solution for having diluted one times or more water is slowly added into
In water, keeping pH is 3 or so, and when neutralizing beginning, every 30 minutes acid addings are primary, and after 4 hours, every 1 hour acid adding is primary, and about 8 is small
When can add all acid, continue stirring 4-8 hours.
1.8 washing
Washing is the salt that acid and generation extra when neutralizing are removed with clear water.
It keeps stirring, it is primary to change within every 1 hour water, changes altogether 10 times or so.The pH value of skin should meet and want when enduring glue after washing
It asks, generally 5.5 or so.
1.9 endure glue
A certain amount of water is first put to glue pot, is heated to enduring 55 DEG C of glue minimum temperature, then pours into the cladding washed
Glue pot, pays attention to pine of hitting a man when he's down, and does not make agglomerating.Then adding water submerges cladding just, is to slowly warm up to endure glue temperature 65-
100 DEG C, pH should be controlled 5.5 or so.
Fresh pig skin endures the control of glue temperature at 55-100 DEG C, and fresh ox-hide control is at 75-100 DEG C.
1.10 boilings suspend, are spraying
Boiling is so that it is generated boiling in the case where negative pressure the method for gelatin vacuum with dedicated boiling granulator
Water for injection is atomized by effect, is sprayed on the gelatin of boiling, so that the little particle of gelatin is bonded to particle through spraying water, is passed through
Droplet size is adjusted to control gelatin corpuscle partial size, porous gelatin corpuscle can be obtained through drying.
Suspension is that gelatin is mixed into lotion with water for injection in proportion, by spraying 50 DEG C of the method penetrating-of the lotion
In 80 DEG C of closed bin, and suitably enters the lotion that negative pressure is sparged into and suspend and dry.
1.11 inner packing
Freeze-dried products are taken out from drying box of freeze dryer, specification as required is cut, and installation verification lot number is errorless, will be wrapped
After table top of installing is sterilized with 75% alcohol wipe, product inner packing is carried out.
Packing machine should all check the upper heating of setting, lower heating, whether seal temperature is set in adds before each packaging
Heat is 80 DEG C ± 5 DEG C, heat-sealing is at 140 DEG C ± 5 DEG C.
Inner packing answers continuous stamping to be no less than 20 empty packages before carrying out product packaging, carries out product packet again after inspection
Dress.
Whether accurate, sealing machine temperature is set in 220 DEG C to verification compound membrane bag stamp, and speed is set as 6 times/min, will be complete
It is packed into compound membrane bag and seals at the product of one layer of inner packing.
1.12 sterilizing
Turnover box is added by GB18280-2000idt ISO 11137 in the interior product wrapped:1995《Healthcare products go out
Bacterium confirmation and conventional control require radiation sterilization》Select 25kGy dosage.
1.13 outer packing
It will sterilize via radiation and examine qualified product to be fitted into the middle packing box for accomplishing fluently lot number together with specification and be put into
Middle packaging is finally packed into big packing case by the quality certification, the good product batch number of big packing case outer cover and sterilization date etc..
Effect experimental examples 1
Biocompatibility is the extremely important performance of biomedical material, to ensure safety of the materials'use after human body
Property, according to, to the biocompatibility test project demand of gelatin product, reference Qi Chen edits in GB/T16886.1-2001《In
Medicine pharmacological experimental method》Beijing：People's Health Publisher, 1994.46-108 test methods provided, by our company's production
Gelatin hemostatic material is impregnated 24 hours with physiological saline by the proportion of 1.25cm/mL, extracting solution is taken to carry out acute toxicity
Test, irritation test, sensitivity test and hemolytic test and have been carried out subcutaneously cell toxicity test with gelatin hemostatic material
Implantation Test.
2.1. sterile
According to《Pharmacopoeia of People's Republic of China》The regulation of 2010 editions two annex XI H is detected, and rule are as a result met
It is fixed：
Product is sterile after Co-60 ray sterilizing.
2.2. bacterial endotoxin
According to《Pharmacopoeia of People's Republic of China》The two annex XI E methods of version in 2010 are detected, and rule are as a result met
It is fixed：
Bacterial endotoxin reaches≤0.5EU/mg.
2.3. systemic acute toxi-city
Leaching liquor is taken to be detected by GB/T16886.11：
Test method：Healthy mice 20 are selected, for weight in 17-23g, male and female are each flat, are randomly divided into experimental group and right
According to group.Take leaching liquor that experimental group small white mouse is injected intraperitoneally, control group injecting normal saline, the upper and lower noon is each primary, injection
Dosage is 0.3mL/10g weight, continuous 7 days, observes its sign situation.
Test result：Toxic reaction is had no in acute toxicity test, small white mouse all survives, weight gain.Experimental group and
Control group weight no significant difference.Illustrate that gelatin hemostatic material used in this test will not cause acute poisoning symptom.
2.4. cytotoxicity
It takes leaching liquor to be detected by leaching liquor method in GB/T16886.5, as a result meets regulation：
Cell toxicity test is the screening test of first stage in medical material Evaluation of Biocompatibility.Nineteen eighty-three, by Mos
Man reports a kind of Fast Evaluation cell Proliferation for the first time and the colorimetric analysis (MTT colorimetric method) of cytotoxicity is wide at present
The general evaluation of its biocompatibility applied to medical material.
Test method：This experiment is using the leaching liquor of MTT colorimetric determination collagen hemostatic material to fibroblast
2, the cytotoxicity of gelatin hemostatic material is evaluated in the influence of 4,7 days opposite proliferation rates.Gelatin hemostatic material 1cm to be measured2It is added
10mL cell culture fluid sets 37 DEG C of standings and takes supernatant as the material leaching liquor of 100% concentration in 24 hours；Cell culture is used again
It is spare that 50% material leaching liquor is made in liquid doubling dilution.
The measurement of cell opposite proliferation rate and Materials Cell toxicity assessment：With the mouse skin of cell culture fluid logarithmic growth phase
It is 6 × 10 that fibroblast (2-3 generation), which is made into concentration,4A/mL cell suspension, every 100 μ L of hole, is inoculated in 96 well culture plates,
Set 37 DEG C, 5%CO2It is cultivated 24 hours in incubator；(200 μ L/ are replaced with the material leaching liquor of 50%, 100% concentration respectively
Hole), using cell culture fluid as blank control, continue to overturn away liquid in 2 holes after setting 37 DEG C of cultures 4 hours, every hole adds
DMSO150 μ L shakes 10min；Enzyme linked immunological instrument measures the absorbance value in every hole, and each group 8 take mean value.Measuring wavelength is
490nm calculates the cell opposite proliferation rate (RGR) of sample by formula R=experimental group OD/ control group OD × 100% later and presses
The following table 1 evaluates the cytotoxicity classification of gelatin hemostatic material.
The cytotoxicity of 1 gelatin hemostatic material of table is classified
| RGR (%) | Cytotoxicity classification |
| ≥100 | 0 |
| 75-99 | I |
| 50-74 | II |
| 25-49 | III |
| 1-24 | IV |
| 0 | V |
Test result：The gelatin hemostatic material leaching liquor of concentration 50%, 100%, 2 days cell opposite proliferation rates may be up to
99% or more, 4 days, 7 days opposite proliferation rates extend declined at any time, but still 80% or more, cytotoxicity is divided into I
Grade.
Cytotoxicity reaches≤1 grade.
2.5. haemolysis
It is detected by contact method in GB/T16886.4, hemolysis rate should be less than 5%, as a result meet regulation：
Test method：Rabbit heart blood 10-20mL is taken, it is that 2%RBC suspension is spare that volume fraction, which is made, in separating red corpuscle.
Test is divided into test product pipe, negative control pipe and positive control pipe, and every group sets 4 parallel pipes.Developmental tube is each concentration leaching liquor pair
The dilution of physiological saline, negative control use physiological saline, and positive control uses distilled water.The corresponding sample of 10mL is added in each pipe
Product after 37 DEG C of water-soluble 30min, respectively plus the RBC suspension of 0.2mL, are stood overnight, centrifuged supernatant exists after 37 DEG C of water-soluble 1h
Colorimetric at 520cm.
Test result：The hemolysis rate of experimental group and physiological saline group is respectively less than 5% in hemolytic test, distilled water group it is molten
Blood rate is 100%.Illustrate that testing gelatin hemostatic material used does not cause hemolytic reaction.
2.6. sensitization of skin
It is detected by maximum dose method in GB/T16886.10：
Test method：Take healthy guinea pig 12, the next day be injected intraperitoneally 0.2mL leaching liquor, continuous 3 times, wherein 6 in for the first time
After injection continuous 14 days by be injected intraperitoneally 2mL leaching liquor；Other 6 21 days intraperitoneal injection 2mL leaching liquors after injecting for the first time.Often
There is useless grab to scratch nose, sneeze, perpendicular hair, twitch, expiratory dyspnea, size after observing 15 minutes, especially final injection after secondary injection
The reaction such as fecal incontinence, body temperature change, shock, death.
Test result：In sensitivity test after guinea pig intraperitoneal injection, whole cavys are survived, experimental group and control group cavy
Behavioral activity situation no significant difference.Illustrate that gelatin hemostatic material used in this test does not lead to body allergic reaction.
Sensitization rate reaches≤8%.
2.7. intradermal stimulation
It takes leaching liquor to be detected by GB/T16886.10, meets regulation：
Test method：Rabbit quadriceps muscle of thigh test injection：New zealand rabbit 10, right hindlimb quadriceps muscle of thigh is test area,
1-2mL leaching liquor is injected, left side corresponding position is injected isometric physiological saline with method and compared, and 48 hours, 14 days, 21 are injected
Test rabbit is put to death in its grouping, and quadriceps muscle of thigh is taken out in dissection, longitudinally slit, observation injection site musculature variation：(1) grade, yin
Property reaction, it is nonirritant, medicine-feeding part with compare position indifference；(+) grade, suspicious reaction, medicine-feeding part musculature is congested,
Diameter is in 0.5cm or so；(++) grade, mild reaction, medicine-feeding part musculature is congested, and diameter is in 1cm or so；(+++) grade, weight
Degree reaction, medicine-feeding part tissue is red and swollen, blue, and gloss disappears, it is seen that downright bad point.Tissue send pathologic finding simultaneously.
Test result：Quadriceps muscle of thigh injects leaching liquor and physiological saline 48 hours, 14 days, 21 days, and each experimental group naked eyes are seen
Tissue is examined without significant reaction；Swelling between tissue striated muscle is seen by tissue pathology checking within 48 hours, but has no apparent inflammatory reaction；
See that rhabdium swelling degree gradually mitigates within 14th day and the 21st day, has no apparent inflammatory reaction, control group and experimental group
The extent of reaction is identical.Test result illustrates that gelatin hemostatic material used in this experiment has no stimulation to deep tissue, does not generate bright
Aobvious tissue reaction.
2.8. Implantation Test
It is tested according to test method as defined in GB/T16886.6：
Test method：Male mouse of kunming 28, weight 25-30g.Under aseptic condition, gelatin hemostatic material is punched
The former piece of diameter 1cm is made in device；Fixed after mouse anesthesia, the disinfection of back center, unhairing, the stringer for cutting off about 0.7cm or so are cut
Mouthful, gelatin hemostatic material is put into right side subcutaneously, it is normal to raise after 2 needle of catgut suture.Postoperative 3,5,7,9 days optional 7 of difference
It visually observes and draws materials after execution and carry out routine histologic inspection.
Test result：Gross examination of skeletal muscle：Postoperative 3 days, it is closer to see that gelatin hemostatic material is attached with substrate, is not easy to uncover, but
It can completely take out, substantially without inflammatory reaction, surrounding materials tissue is without necrosis, abscess；5 days after operation, gelatin hemostatic material have dropped
Solve thinning, surface is wrapped up by a few fibres film, and tunica fibrosa is wrapped up on removal surface, and material is complete, and surface is smooth；Postoperative 7 days, gelatin
Hemostatic material it is obvious it is thinning, become smaller, material is micro- in faint yellow, and surface is smooth；Postoperative 9 days, material was substantially completely degraded, on a small quantity
Residual fraction has been not easy completely to separate.Histomorphological：Postoperative 3 days, it is seen that have a little neutral grain in gelatin hemostatic material
Inflammatory cell infiltration based on cell, lymphocyte, gelatin hemostatic material reticular structure are clear；Postoperative 9 days, gelatin hemostatic material
It fully absorbs, is replaced fibrous connective tissue.Each time has no tissue degeneratiaon, necrosis.
After muscular grafting 7 days, the inflammatory cell extent of reaction≤IV grades；After implantation 15 days, the inflammatory cell extent of reaction≤III
Grade；Implantation 30 days after, the inflammatory cell extent of reaction≤II grade, and around be no different paradoxical reaction 6 weeks after this product be absorbed.
2.9. genetoxic
It is tested according to test method as defined in GB/T16886.3, as a result meets regulation：
Hereditary-less toxicity.
2.10. degradation
Enzymatic isolation method is examined by GB/T16287-1996 method, in product starch at a temperature of 37 DEG C ± 2 DEG C, be placed in containing
In the physiological saline of a- amylase and carbohydrase after 72 hours, under a- amylase and saccharification enzyme effect, it is converted into glucose,
Conversion ratio is equal to degradation rate.
Through examining, product is subcutaneously implanted 6 weeks and is degraded and absorbed, and histologic reaction is good.
Product does not release the substance that any couple of patient generates side effect, meets the biology that GB/T16886.1 is provided and comments
Valence guide.Gelatin hemostatic material provided by the invention has good biocompatibility, the nontoxic secondary work of inside and outside safety experiment
With.
Effect experimental examples 2
The physicochemical property of product and the stability of biological efficiency are to determine the important symbol of keeping life.This product ginseng
It according to same kind of products at abroad and the provisions of the relevant regulations issued by the State, will fix tentatively 2 years validity period, while same batch products will be carried out 4 years by a definite date
Real-time tracing research, research contents is as follows：
3.1. Testing index
3.1.1. the physical property detection of gelatin hemostatic material
3.1.1.1. the appearance of gelatin hemostatic material and surface texture (annual periodically primary)：
The appearance of gelatin hemostatic material under natural light by visually observing.Surface texture is seen by scanning electron microscope (SEM)
It examines, is completed by central laboratory of Yangzhou University.As shown in (a) and (b) of Fig. 1.
3.1.1.2. water absorbing capacity (every half a year periodically carries out once)：
Gelatin hemostatic material 5 are taken, electronic balance precision weighs every tablet quality.It immerses in 20mL room temperature (25-30 DEG C) water,
After suctioning moisture, one jiao gently being clamped with tweezers, is left the water after draining 1min, electronic balance weighing obtains every water suction
Quality afterwards.Water absorbing capacity is calculated by method：
Quality/sample quality after water absorbing capacity (again)=water suction
3.1.1.3. mass per volume (apparent density) (every half a year periodically carries out once)：
Gelatin hemostatic material 5 are taken, length, width and the height of accurate measurement every calculate sample volume；Electronics day
It is flat to weigh quality, the quality in hemostatic material unit volume is calculated, mean value is taken.
3.1.2. the chemical property detection (annual periodically to carry out once) of gelatin hemostatic material
3.1.2.1.pH value measurement
Take gelatin hemostatic material 5, every tear after be immersed in 30min in 15mL distilled water, according to《Chinese people's republicanism
State's pharmacopeia》The measurement of method as defined in two annex.
3.1.2.2. total protein and hydroxyproline content measure
Total protein content measurement measures examination using the biuret method total protein content of Shanghai Rongsheng Bioisystech Co., Ltd
Agent box, standard protein use the gelatin of Sigma company, are dissolved after accurately weighing with spirit of vinegar.Gelatin hemostatic material sample is used
The dissolution of 20mL spirit of vinegar, takes lysate to measure.
Calculation method：
Total protein content=total protein measured value/gelatin hemostatic material quality × 100%
Hydroxyproline content measurement uses chloramine-t method.The hydroxyproline determination of Bioengineering Research Institute is built up using Nanjing
Kit.6N HCl tube sealing is added after gelatin hemostatic material sample precise, 110 DEG C of hydrolysis take hydrolyzate to measure.
Calculation method：
Hydroxyproline content=hydroxyproline determination value/total protein measured value × 100%
3.1.3. gelatin hemostatic material biological property detects
3.1.3.1. liver hemostasis and in vivo Implant experiment (each year periodically carries out one-time detection)
New zealand white rabbit 15, weight 2-2.5kg are taken, is organized at two in same lobectomy of liver liver 1cm, oozing of blood is formed
The surface of a wound uses gelatin hemostatic material and gelatin hemostatic material (production of Nanjing third pharmaceutical factory) apply pressure surface of a wound, when record stops blooding respectively
Between；It is sutured after hemostasis at four angles of hemostatic material and the liver surface of a wound, its absorption degradation situation of routine observation simultaneously carries out pathology inspection
It surveys.
3.1.3.2. gelatin hemostatic material Sterility testing (annual periodically to carry out one-time detection)
Testing result：
The testing result of gelatin hemostatic material physical property is as shown in table 2 below：
The testing result of 2 gelatin hemostatic material physical property of table
The testing result of gelatin hemostatic material chemical property is as shown in table 3 below：
The testing result of 3 gelatin hemostatic material chemical property of table
| Detection time | Testing index | Testing result |
| 2014.12 | PH value measurement | 5.35±0.31 |
| 2014.12 | Total protein content (%) | 87.3±4.22 |
| 2014.12 | Hydroxyproline content (%) | 10.78±0.56 |
| 2015.12 | PH value measurement | 5.31±0.21 |
| 2015.12 | Total protein content (%) | 86.5±4.32 |
| 2015.12 | Hydroxyproline content (%) | 10.62±0.54 |
| 2016.12 | PH value measurement | 5.00±0.49 |
| 2016.12 | Total protein content (%) | 87.5±4.32 |
| 2016.12 | Hydroxyproline content (%) | 10.54±0.50 |
| 2017.12 | PH value measurement | 5.15±0.30 |
| 2017.12 | Total protein content (%) | 88.5±4.01 |
| 2017.12 | Hydroxyproline content (%) | 10.16±0.56 |
The testing result of gelatin hemostatic material biological property is as shown in table 4 below：
The testing result of 4 gelatin hemostatic material biological property of table
| Detection time | Testing index | Testing result |
| 2014.12 | It answers sterile | It is sterile |
| 2015.12 | It answers sterile | It is sterile |
The invention is not limited to above embodiment, if not departing from the present invention to various changes or modifications of the invention
Spirit and scope, if these modification and variations belong within the scope of claim and equivalent technologies of the invention, then this hair
It is bright to be also intended to encompass these changes and change.
Claims (10)
1. a kind of preparation process of gelatin hemostatic material, which is characterized in that include the following steps：
(1) gelatine starting material carries out pre-treatment；
(2) match ash, pre- liming, chopping, liming, move back ash；
(3) it neutralizes, wash, endure glue；
(4) gelatin hemostatic material is prepared；
(5) dress, sterilizing, outer packing is wrapped inside in gelatin hemostatic material.
2. preparation process according to claim 1, it is characterised in that：In step (1), the pre-treatment is：To be not of the same race
Class, different parts cladding separately handle, be cut into the strip of 10cm wide；The cladding be selected from dry hide or fresh hide, ox-hide or pigskin,
One of cattle hide or buffalo hide, upper splitting or lower splitting, scalp, foot skin are a variety of.
3. preparation process according to claim 1, it is characterised in that：It is described to be with ash in step (2)：By quick lime elder generation
Water is added to be made into thick slurry, 1 kilogram of lime adds 1.2-1.5 kilograms of water, and it stores 12-18 days or so, is diluted with water, filters out coarse granule,
It is spare；The pre- liming is：It is impregnated cladding 2-3 days with the limewash containing about 1% calcium oxide.
4. preparation process according to claim 1, it is characterised in that：In step (2), the liming is：With lime water logging
Steep cladding；When liming, limewash internal oxidition calcium content is controlled in 2-4%；The ash that moves back is：Under constant stirring, every 30 minutes
It is primary to change water, total 10-15 times or so；It is primary to change water within every 1 hour later；The ratio of raw material and water should be 1: 6 or so every time；24-
It completes within 36 hours to move back ash, pH is 9.5 or so.
5. preparation process according to claim 1, it is characterised in that：In step (3), the neutralization is：First plus water makes skin
Expect submerged in water, starts stirring, the hydrochloric acid solution for having diluted one times or more water is slowly added into water, keeping pH is 3 or so,
When neutralizing beginning, every 30 minutes acid addings are primary, and after 4 hours, every 1 hour acid adding is primary, add all acid within about 8 hours, continue to stir
It mixes 4-8 hours.
6. preparation process according to claim 1, it is characterised in that：In step (3), the glue of enduring is：It first puts a certain amount of
Water to glue pot, be heated to enduring 55 DEG C of glue minimum temperature, the cladding washed then poured into glue pot, adding water makes cladding
It just submerges, is to slowly warm up to endure 65-100 DEG C of glue temperature, pH should be controlled 5.5 or so.
7. preparation process according to claim 1, it is characterised in that：It is described to prepare gelatin hemostatic material tool in step (4)
Body step is：Gelatin is subjected to ultrasonic wave homogeneous, the methods of the assembly after homogeneous being boiled, is suspended, is spraying, it is more to be made
Hole particle is to get gelatin hemostatic material.
8. preparation process according to claim 7, it is characterised in that：In step (4), the boiling is the method with vacuum
So that it is generated boiling effect in the case where negative pressure, water for injection is atomized, is sprayed on the gelatin of boiling, the little particle of gelatin is made
It is bonded to particle through spraying water, gelatin corpuscle partial size is controlled by adjusting droplet size, porous gelatin can be obtained through drying
Particle.
9. preparation process according to claim 7, it is characterised in that：In step (4), it is described suspension be by gelatin in proportion
It is mixed into lotion with water for injection, which is sprayed into spraying method in 50 DEG C -80 DEG C of closed bin, and suitably enter negative
The lotion being sparged into is pressed to suspend and dry.
10. a kind of gelatin hemostatic material, it is characterised in that：It is made by the described in any item preparation processes of claim 1-9.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101361986A (en) * | 2007-08-09 | 2009-02-11 | 美国淀粉医疗公司 | Modified starch absorbable hemostasia material and preparation method thereof |
| CN101862469A (en) * | 2010-05-28 | 2010-10-20 | 武汉锐尔生物科技有限公司 | Chitosan derivative quick hemostasis granules and preparation method thereof |
| CN102363715A (en) * | 2011-11-14 | 2012-02-29 | 广西大学 | Method for preparing gelatin |
| CN102406956A (en) * | 2011-03-09 | 2012-04-11 | 天津爱勒易医药材料有限公司 | Starch hemostatic microsphere and preparation method thereof |
| CN104231943A (en) * | 2013-06-20 | 2014-12-24 | 任利娜 | Method for manufacturing gelatin |
| CN105597144A (en) * | 2015-12-31 | 2016-05-25 | 北京湃生生物科技有限公司 | Absorbable collagen styptic powder and preparing method thereof |
| CN105688269A (en) * | 2016-02-03 | 2016-06-22 | 广州迈普再生医学科技有限公司 | Modified gelatin hemostatic material and preparation method thereof |
| CN106634623A (en) * | 2016-09-20 | 2017-05-10 | 苏州吉利鼎海洋生物科技有限公司 | Production process for gelatin |
-
2018
- 2018-07-23 CN CN201810813845.0A patent/CN108815563A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101361986A (en) * | 2007-08-09 | 2009-02-11 | 美国淀粉医疗公司 | Modified starch absorbable hemostasia material and preparation method thereof |
| CN101862469A (en) * | 2010-05-28 | 2010-10-20 | 武汉锐尔生物科技有限公司 | Chitosan derivative quick hemostasis granules and preparation method thereof |
| CN102406956A (en) * | 2011-03-09 | 2012-04-11 | 天津爱勒易医药材料有限公司 | Starch hemostatic microsphere and preparation method thereof |
| CN102363715A (en) * | 2011-11-14 | 2012-02-29 | 广西大学 | Method for preparing gelatin |
| CN104231943A (en) * | 2013-06-20 | 2014-12-24 | 任利娜 | Method for manufacturing gelatin |
| CN105597144A (en) * | 2015-12-31 | 2016-05-25 | 北京湃生生物科技有限公司 | Absorbable collagen styptic powder and preparing method thereof |
| CN105688269A (en) * | 2016-02-03 | 2016-06-22 | 广州迈普再生医学科技有限公司 | Modified gelatin hemostatic material and preparation method thereof |
| CN106634623A (en) * | 2016-09-20 | 2017-05-10 | 苏州吉利鼎海洋生物科技有限公司 | Production process for gelatin |
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