CN115337456B - High permeability solution and application thereof - Google Patents
High permeability solution and application thereof Download PDFInfo
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- CN115337456B CN115337456B CN202210942336.4A CN202210942336A CN115337456B CN 115337456 B CN115337456 B CN 115337456B CN 202210942336 A CN202210942336 A CN 202210942336A CN 115337456 B CN115337456 B CN 115337456B
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/362—Skin, e.g. dermal papillae
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3625—Vascular tissue, e.g. heart valves
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
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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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
Abstract
The invention discloses a high-permeability solution and application thereof, wherein the high-permeability solution comprises the following components: monosaccharides, disaccharides and/or sugar alcohols; and biological polysaccharides. The invention adopts glucose, fructose and/or sucrose as solute components of the high-permeability solution, and the biological polysaccharide is added, so that the dehydration process is milder, and the dehydration process is not needed to be performed once, so that the size of the dehydrated biological dry valve is kept as much as possible.
Description
Technical Field
The invention relates to the technical field of biomedical materials, and further relates to a high-permeability solution and application thereof.
Background
Heart valve disease is a type of heart disease mainly faced in China. Because the biological valve has good biocompatibility and durability, the anticoagulation treatment is not required for a long time, so that the application of the biological valve is gradually improved.
Biological valves used clinically are stored in glutaraldehyde solution, and glutaraldehyde not only can kill microorganisms, but also has good crosslinking effect, so that the biological membrane structure is stable. At the same time, the following problems are also present: 1. the aldehyde group calcifies the biological valve, which affects the service life 2, the inconvenient storage of the biological valve, the high transportation cost 3, the rinsing requirement before clinical use and the complex operation. In order to solve the problems, the traditional mode of storing the biological valve by using a liquid medium is changed, the biological valve is dehydrated by a chemical solution and is dried by a physical mode, and the obtained biological dry valve not only avoids the problems caused by soaking the biological valve in glutaraldehyde solution, but also can maintain good durability and blood flow dynamics of the wet biological valve.
European patent EP2606723A1 discloses a method for preparing a bio-dry valve, which uses an ethanol solution of mannitol as a permeate, uses a concentration gradient difference formed by the permeate to dewater, uses the concentration difference to perform molecular diffusion, but has strong permeation, and when the ethanol gradient is permeated, the bio-valve tissue is easy to be deformed due to severe folds caused by concentration jump mutation; and ethanol has volatility, and the solute is quickly volatilized after being replaced into the biological valve tissue, so that the biological valve tissue is dehydrated too quickly to generate hardening, brittleness and other technical problems.
Disclosure of Invention
Aiming at the technical problem that the biological dry valve prepared by the prior art adopts ethanol solution of mannitol as penetrating fluid, which is very easy to cause the biological valve tissue to be severely wrinkled and deformed, the invention aims to provide a high-permeability solution for preparing the biological dry valve, which comprises the following components:
the mass concentration of the monosaccharide, the disaccharide and/or the sugar alcohol is 20-30 percent;
and biological polysaccharide with mass concentration of 20-30%.
In the high osmotic solution of the present invention, the monosaccharides, dimeric sugars and/or sugar alcohols form a gradient concentration to dehydrate the tissue; the biological polysaccharide is added into the high-permeability solution as a wetting humectant to moisturize the dehydrated biological valve.
In a preferred embodiment of the invention, the mass concentration of the monosaccharides, disaccharides and/or sugar alcohols is 20-30%, preferably 22-28%, more preferably 25%;
the mass concentration of the biological polysaccharide is 20-30%, preferably 22-28%, more preferably 25%.
In a preferred embodiment of the present invention,
the monosaccharide and the dimeric sugar are selected from one or more of glucose, fructose and sucrose; the sugar alcohol is selected from mannitol.
The biological polysaccharide is one or more selected from chitosan, trehalose, tremella polysaccharide, dextran and hyaluronic acid.
It is another object of the present invention to provide a use of a high permeability solution for the preparation of a bio-dry valve, wherein the high permeability solution comprises:
the mass concentration of the monosaccharide, the disaccharide and/or the sugar alcohol is 20-30 percent;
and biological polysaccharide with mass concentration of 20-30%.
In a preferred embodiment of the present invention,
the mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 20-30%, preferably 22-28%, more preferably 25%;
the mass concentration of the biological polysaccharide is 20-30%, preferably 22-28%, more preferably 25%.
In a preferred embodiment of the present invention, the monosaccharide and the disaccharide are selected from one or more of glucose, fructose and sucrose; the sugar alcohol is selected from mannitol.
In a preferred embodiment of the present invention, the biological polysaccharide is selected from one or more of chitosan, trehalose, tremella polysaccharide, dextran, and hyaluronic acid.
In a preferred embodiment of the present invention, the bio-dry valve is selected from one or more of pericardium, dermis and blood vessel.
It is a further object of the present invention to provide a method of preparing a biological dry valve, the method being a two-step dehydration process comprising:
a first dehydration step of immersing the crosslinked biological valve in a high-permeability solution to remove part of free water and obtain a first dehydrated biological valve;
a secondary dehydration step, wherein the primary dehydrated biological valve is freeze-dried in vacuum to remove the residual free water to obtain the biological dry valve.
In a preferred embodiment, the method further comprises:
and a sealing and moisturizing step, wherein after the primary dewatering step and before the secondary dewatering step, the primary dewatering biological valve is soaked in a sealing agent to seal the primary dewatering biological valve.
In a preferred embodiment, the method further comprises:
and an infrared radiation step, wherein after the closed moisturizing step and before the secondary dewatering step, the closed biological valve is irradiated with infrared rays to improve the secondary dewatering rate.
In the first dehydration step, the soaking time is 8 to 72 hours, preferably 16 to 36 hours, more preferably 24 to 28 hours.
In the first dewatering step, the high-permeability solution includes:
monosaccharides, disaccharides and/or sugar alcohols;
and biological polysaccharides.
The invention utilizes the concentration difference of the high-permeability solution in the biological valve tissue and outside the tissue to enable part or all of water in the biological valve tissue to permeate into the high-permeability solution so as to remove part or all of free water in the biological valve. Because the water content in the hypertonic solution is lower than the free water content in the biological valve tissue, a concentration gradient of water is formed at the interface of the high-permeability solution and the biological valve, and the free water in the biological valve tissue moves from a high concentration area to a low concentration area, namely the water removal effect of the biological valve is shown.
In a preferred embodiment, the mass concentration of the monosaccharides, disaccharides and/or sugar alcohols is 20-30%, preferably 22-28%, more preferably 25%; the mass concentration of the biological polysaccharide is 20-30%, preferably 22-28%, more preferably 25%.
In a preferred embodiment, the monosaccharide and the disaccharide are selected from one or more of glucose, fructose and sucrose; the sugar alcohol is selected from mannitol. The biological polysaccharide is selected from one or more of chitosan, trehalose, tremella polysaccharide, dextran and hyaluronic acid.
In a preferred embodiment, in the secondary dewatering step,
the vacuum freeze drying is that the vacuum freeze drying is carried out by pre-freezing for 8-20 hours, preferably 10-16 hours, more preferably 12 hours at-60 to-50 ℃, preferably-55 ℃, then vacuumizing to 6-10 Pa, preferably 8Pa, and drying for 16-40 hours, preferably 20-30 hours, more preferably 24 hours at normal temperature.
In the closed moisturizing step, the biological valve is immersed in the sealing agent at 50-60 ℃ for 2-24 hours, preferably 4-12 hours. The blocking agent is selected from one or more of mineral oil and animal fat. The mineral oil is selected from paraffin oil; and/or the animal fat is selected from lanolin. The paraffin oil is C18-30 paraffin oil, preferably C20-25 paraffin oil; the lanolin is lanolin with molecular weight 104.10.
In the infrared radiation step, the closed biological valve is irradiated with infrared rays having a power density of 350 to 450w/g, preferably 400w/g, at a temperature of 70 to 90 ℃, preferably 80 ℃, for 3 to 5 hours, preferably 4 hours, at an irradiation distance of 100 to 150mm, preferably 120 mm.
A washing step may be further included before the first dehydrating step: the crosslinked biological valve is washed with physiological saline for 2 to 5 times, preferably 3 times, for 4 to 10 minutes, preferably 5 minutes each time.
The biological valve is selected from one or more of pericardium, dermis and blood vessel.
The method further comprises the steps of:
dry valve preservation step: the biological dry valve is stored in a polyethylene bottle, the inner wall of the polyethylene bottle is coated with a coating, and the raw materials of the coating comprise 65-75 mass percent, preferably 70 mass percent, of hydroxyproline and/or glycine, and 25-35 mass percent, preferably 30 mass percent, of polyvinyl alcohol.
The invention also provides a biological dry valve prepared by the method.
The combination water of the biological dry valve is 30-33%.
The biological dry valve is stored in a polyethylene bottle, the inner wall of the polyethylene bottle is coated with a coating, and the raw materials of the coating comprise 65-75 mass percent, preferably 70 mass percent, of hydroxyproline and/or glycine, and 25-35 mass percent, preferably 30 mass percent, of polyvinyl alcohol.
Compared with the prior art, the invention has the beneficial effects that:
1) The invention adopts a two-step dehydration method, wherein partial free water is removed in the high-permeability solution in the first step, and the rest free water is removed by continuous freeze drying in the second step.
2) The invention adopts glucose, fructose and/or sucrose as solute components of the high-permeability solution, and the biological polysaccharide is added, so that the dehydration process is milder, and the dehydration process is not needed to be performed once, so that the size of the dehydrated biological dry valve is kept as much as possible.
3) The invention adopts glucose, fructose and/or sucrose as solute components of high-permeability solution, the molecular weight (such as glucose molecular weight 180.16) is larger than the molecular weight (45) of ethanol, and the viscosity (such as glucose viscosity 30 Pa.s) of high-concentration sugar solution is larger than the viscosity (1.096 pa.s) of ethanol, so that the permeation speed is slower than that of ethanol, and the permeation effect is milder. The sugar solution can also avoid other problems caused by using ethanol, such as ethanol has volatility, and the solute is quickly volatilized after being replaced into the tissue, so that the tissue is dehydrated too quickly to be hard and brittle; in addition, when ethanol is infiltrated in gradient, concentration jump mutation exists, and the tissue is easy to generate severe folds.
4) The biological dry valve after free water removal retains a proper amount of bound water. The biological polysaccharide is used as a moistening humectant, contains hydroxyl, acetyl and amino, is strongly combined with water to prevent water evaporation, so that tissue cells are flexible and softened, and the moisture absorption and preservation performance is good.
5) The invention also uses a sealing agent to carry out sealing and moisture preservation before secondary dehydration, and a layer of insoluble lipid is wrapped on the surface of the biological dry valve. The insoluble lipids form an additional lubricating film layer on the biological dry valve, wrap the tissues, and prevent water loss through sealing action so as to prevent water evaporation. The biological polysaccharide is used as a wetting humectant and the insoluble lipid is used as a sealing humectant in combination, so that a better moisturizing effect can be achieved.
6) Irradiation with infrared rays may be used before the secondary dehydration to increase the removal rate of the secondary dehydration.
7) The characteristics of stable property and difficult damage of the combined water are utilized, and the biological dry valve keeps certain combined water while free water is removed by secondary dehydration. The water content of the biological dry valve after secondary dehydration is about 30%, the water content of the biological valve which is rehydrated in the biological saline for 5 minutes can be restored to about 70% of the initial state, and compared with the condition that the washing time of the biological valve is about 30 minutes before the traditional biological valve is used, the surgical time can be greatly shortened by the step alone.
8) After the inner wall of the polyethylene bottle is coated with a coating, the polyethylene bottle is cooled to room temperature to form rubber-like shape, and is not easy to fall off. The hydroxyproline absorbs water to maintain the water content of the biological dry valve at 30% -33%. The hydroxyproline can absorb redundant moisture in the air, so that the prepared biological dry valve can keep the moisture content stable in the storage process without excessively absorbing the moisture in the air.
9) The biological dry valve reduces aldehyde residue, is stored in a dry mode (does not need to be stored in a solution), is convenient to transport, does not need to be rinsed before clinical use, and can be used after being hydrated in normal saline.
10 The preparation method of the biological dry valve provided by the invention can also be used for preparing valves, cerebral dura mater, intestinal mucosa, ligaments, tendons, sclera and valved pipelines.
Detailed Description
Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention. It should be noted that the following embodiments and features in the embodiments may be combined with each other without conflict.
Examples 1 to 8
And (3) cleaning: the crosslinked biological valve (bovine pericardium) was cut into a round shape with a diameter of 2cm, 4cm, 6cm, 8cm, 10cm and a thickness of about 0.3mm, and the biological valve was washed with physiological saline for N1 times each time t 1.
A first dehydration step: weighing sugar and biological polysaccharide, and dissolving in water to obtain high-permeability solution (the components and the dosage are shown in Table 1). Immersing the crosslinked biological valve in the high-permeability solution for t2 time, and removing part of free water to obtain the first dehydrated biological valve.
And (3) a closed moisturizing step: the first dehydrated biological valve was immersed in 500mL of blocking agent at T1 temperature for a period of time T3.
An infrared radiation step: the closed biological valve is irradiated with infrared rays of power density ρ at a temperature T2 and an irradiation distance D for a time T4.
And (3) a secondary dehydration step: pre-freezing the biological valve at T3 for T5 hours, then transferring to room temperature T4, vacuumizing to P1, drying for T6 hours, and sublimating the water separated out from the surface of the biological valve to obtain the biological dry valve
And (3) a storage step: placing the dehydrated biological dry valve in a polyethylene bottle with a coating (the coating contains hydroxyproline and polyvinyl alcohol with certain mass fractions) in advance, sealing and preserving t7, and detecting the moisture content of the dehydrated biological valve.
The process parameters are shown in table 2.
TABLE 1 Components and content of high osmotic solutions
Table 2 process parameters for examples 1-8 and comparative example 1
TABLE 2 Process parameters for examples 1-2 and comparative example 1
Comparative examples
1. Selecting a crosslinked biological valve (bovine pericardium), preparing into a round shape with diameters of 2cm, 4cm, 6cm, 8cm and 10cm and thicknesses of about 0.3mm, and cleaning the biological valve with physiological saline for 5 times and 5 minutes each time for later use.
2. Preparing a dry solution, taking 250mL of ethanol solution containing 70% of glycerol as an osmotic solution, immersing the crosslinked biological valve in the osmotic solution for 24 hours, taking out, replacing the same osmotic solution, and repeating for one time to obtain the dehydrated biological valve.
3. Vacuum packaging the dehydrated biological valve, and measuring the moisture content in the biological valve after a certain time.
Performance test examples
The maximum tensile force and the breaking force of the crosslinked biological valve, the dehydrated and dried biological valve, and the hydrated biological valve (valve: physiological saline (volume ratio) =1:100, dry valve completely immersed for 5 minutes) were measured, respectively.
The testing method comprises the following steps: the tensile test (as in Table 3) was carried out according to the conventional method using a universal mechanical tester at a tensile rate of 25mm/min until the test piece failed to break (as in Table 4).
TABLE 3 tensile strength test data (MPa)
TABLE 4 elongation at break test data (%)
As can be seen from tables 3 and 4, the tensile strength and the elongation at break of the crosslinked biological valves were reduced to different degrees after dehydration and drying, but the biological dry valves prepared in the comparative examples were reduced to a greater extent, for example, the tensile strength was reduced by less than 10% for the biological dry valves prepared in examples 1 to 4, and the tensile strength was reduced by more than 18% for the biological dry valves prepared in the comparative examples. The elongation at break of the bio-dry valves prepared in examples 1-4 was reduced by about 40%, while the tensile strength of the bio-dry valves obtained in the comparative examples was reduced by 54%, which is significantly easier to break than the bio-dry valves prepared in examples 1-4. From tables 3 and 4, it can be found that the tensile strength and elongation at break test data of the biological valve after hydration of the biological dry valve of the present invention are superior to those of the comparative example. This indicates that the mechanical strength effect is more pronounced after hydration of the dehydrated biological valve.
The tensile strength and the elongation at break of the biological dry valve prepared by the method are both improved after hydration, and the tensile strength and the elongation at break of the biological dry valve prepared by the method in the examples 1-4 are both higher than those of the biological valve after crosslinking, namely the biological valve prepared by the method is superior to those of the biological wet valve prepared by the traditional glutaraldehyde crosslinking after implantation into a human body. The tensile strength and the elongation at break of the biological valve obtained by the biological dry valve obtained by the comparative example are lower than those of the biological valve obtained by crosslinking, which indicates that the strength of the biological valve obtained by the comparative example after hydration is not completely recovered.
Moisture test examples
After the biological dry valve is sealed for a period of time, the water content (%) of the biological dry valve is tested, the biological dry valve is weighed by an analytical balance to obtain W1, the biological dry valve is placed in an electrothermal constant-temperature blast drying oven for drying at 80 ℃ for 24 hours, and the biological dry valve is cooled to room temperature and constant weight, and then is weighed again to obtain W2. The water content was calculated as shown in table 5.
TABLE 5 moisture content after seal time (wt%)
As is clear from Table 5, the biological dry valves of examples 1-4 prepared according to the present invention were stable in the range of 30-32wt% without significant change in moisture during 0-24 months of sealing, indicating that the dry storage method can stabilize the moisture content. The moisture content of the biological dry valve prepared in the comparative example is 30.1% when the preparation is finished, the moisture content of the biological dry valve can be kept between 30% and 32% within 12 months, and the moisture content of the biological dry valve exceeds 33% after 18 months of storage, and even the moisture content is up to 36.5% after 24 months, so that the microbial reproduction is obviously accelerated after the moisture content is increased, and the performance of the product is affected.
Biological valve dimensional change testing
The biological valves having diameters of 8cm after crosslinking were measured, respectively, and the biological dry valves prepared using the biological valves, and the biological valves after hydration were soaked in physiological saline (valve: physiological saline=1:100 (volume ratio), the dry valves were completely immersed therein for 5 minutes) and the diameter and thickness were measured (cm, mean ± standard deviation), respectively, using calipers, as shown in tables 6 and 7, respectively.
TABLE 6 diameter Change (cm) before and after hydration
As shown in table 6, the diameters of the biological valves in examples 1 to 4 prepared by the present invention were slightly reduced based on the biological valve after cross-linking (before water removal), and were controlled to be within 1%, the diameters of the biological valves after hydration were recovered to a certain extent, and compared with the biological valve after cross-linking, the diameter reduction range of the biological valve after hydration was less than 0.25%, and the biological valve was recovered to the original level after hydration, so that the valve could basically maintain the skeleton structure of the biological valve after cross-linking. In the comparative example, the diameter of the prepared biological dry valve is reduced by more than 5%, and after hydration, the diameter is reduced to about 2.75% although some recovery is achieved, which indicates that the valve skeleton is damaged in the dehydration process of the biological valve.
TABLE 7 thickness variation before and after hydration
As can be seen from Table 7, the thicknesses of the biological valves in examples 1-4 prepared according to the present invention were not significantly changed after hydration based on the biological valve after crosslinking (before water removal). In the comparative example, the thickness of the prepared biological dry valve is reduced by about 20%, and after hydration, the biological valve thickness is recovered to a certain extent, but the thickness is still reduced by about 16% relative to the biological valve after crosslinking. From tables 6 and 7, no significant change in the diameter and thickness of the hydrated biological valve compared to that after cross-linking was found under the present invention, indicating that the dehydration of the high osmotic solution maintained the dimensional stability of the biological valve.
The specific embodiments described herein are offered by way of example only to illustrate the spirit of the invention. Those skilled in the art may make various modifications or additions to the described embodiments or substitutions thereof without departing from the spirit of the invention or exceeding the scope of the invention as defined in the accompanying claims.
Claims (12)
1. A method of making a biological dry valve, the method being a two-step dehydration process comprising: a first dehydration step of immersing the crosslinked biological valve in a high-permeability solution to remove part of free water and obtain a first dehydrated biological valve;
a secondary dehydration step of freeze-drying the first dehydrated biological valve in vacuum to remove the remaining free water to obtain the biological dry valve;
the high permeability solution comprises:
monosaccharides, disaccharides and/or sugar alcohols;
and biological polysaccharides;
the mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 20-30%;
the mass concentration of the biological polysaccharide is 20-30%.
2. The method of claim 1, wherein
The mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 22-28%;
the mass concentration of the biological polysaccharide is 22-28%.
3. The method of claim 2, wherein
The mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 25%;
the mass concentration of the biological polysaccharide is 25%.
4. The method of claim 1, wherein
The monosaccharide and the dimeric sugar are selected from one or more of glucose, fructose and sucrose; the sugar alcohol is selected from mannitol.
5. The method of claim 1, wherein
The biological polysaccharide is selected from one or more of chitosan, trehalose, tremella polysaccharide, dextran and hyaluronic acid.
6. The application of the high-permeability solution in preparing the biological dry valve is characterized in that the preparation method of the biological dry valve is a two-step dehydration method, and the method comprises the following steps:
a first dehydration step of immersing the crosslinked biological valve in a high-permeability solution to remove part of free water and obtain a first dehydrated biological valve;
a secondary dehydration step of freeze-drying the first dehydrated biological valve in vacuum to remove the remaining free water to obtain the biological dry valve;
the high permeability solution comprises:
monosaccharides, disaccharides and/or sugar alcohols;
and biological polysaccharides;
the mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 20-30%;
the mass concentration of the biological polysaccharide is 20-30%.
7. The use according to claim 6, wherein
The mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 20-30%;
the mass concentration of the biological polysaccharide is 20-30%.
8. The use according to claim 7, wherein
The mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 22-28%;
the mass concentration of the biological polysaccharide is 22-28%.
9. The use according to claim 8, wherein
The mass concentration of the monosaccharide, the dimeric sugar and/or the sugar alcohol is 25%;
the mass concentration of the biological polysaccharide is 25%.
10. The use according to claim 6, wherein
The monosaccharide and the dimeric sugar are selected from one or more of glucose, fructose and sucrose; the sugar alcohol is selected from mannitol.
11. The use according to claim 6, wherein
The biological polysaccharide is selected from one or more of chitosan, trehalose, tremella polysaccharide, dextran and hyaluronic acid.
12. The use according to claim 6, characterized in that said biological dry valve is selected from one or more of pericardium, dermis and blood vessels.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210942336.4A CN115337456B (en) | 2022-08-08 | 2022-08-08 | High permeability solution and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210942336.4A CN115337456B (en) | 2022-08-08 | 2022-08-08 | High permeability solution and application thereof |
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| Publication Number | Publication Date |
|---|---|
| CN115337456A CN115337456A (en) | 2022-11-15 |
| CN115337456B true CN115337456B (en) | 2023-09-15 |
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