CN114452435A

CN114452435A - High-affinity liquid dressing capable of being rapidly effective

Info

Publication number: CN114452435A
Application number: CN202111349317.2A
Authority: CN
Inventors: 张劲松; 朱礼飞; 王金娈; 张玉; 张宇辰
Original assignee: Zhejiang Lanzhi Biotechnology Co ltd
Current assignee: Zhejiang Lanzhi Biotechnology Co ltd
Priority date: 2021-11-15
Filing date: 2021-11-15
Publication date: 2022-05-10
Anticipated expiration: 2041-11-15
Also published as: CN114452435B

Abstract

The invention discloses a high-affinity liquid dressing capable of taking effect quickly, and the formula of the high-affinity liquid dressing capable of taking effect quickly comprises the following components: 1.3-2.5% of composite bacteriostatic agent, 0.2-1.5% of film-forming agent, 0.02-0.1% of pain-relieving agent, 8-10% of calcium and silicon ion bioactive buffer solution, 0.5-20% of modified bioactive glass loaded molecular sieve, 1.2-6% of humectant, 0.2-1.5% of anhydrous ethanol and the balance of deionized water; the compound bacteriostatic agent is one of NAGO VEC or NAGO VAC plant extraction bacteriostatic agent and octenidine hydrochloride, polyhexamethylene biguanide, at least one of poly biguanide is compounded to form. Through the mode, the wound dressing has good biocompatibility, can form an antibacterial protection layer on the surface of a wound, promotes quick liquid absorption, hemostasis and accelerated healing of the wound, is particularly suitable for various acute wounds and cooperative nursing after debridement of a chronic wound, and can be made into finished products including but not limited to mechanical-type functional dressings and disinfection articles for eliminating type numbers.

Description

High-affinity liquid dressing capable of being rapidly effective

Technical Field

The invention relates to the field of medical dressings, in particular to a high-affinity liquid dressing capable of quickly taking effect.

Background

The repair of the damaged wound surface of a body caused by mechanical, physical, chemical, biological or pathological reasons is an old problem in medicine, and the traditional way is that dressings such as gauze, cotton pads and plaster cover the wound to assist the healing of the wound. However, the traditional method has slow healing speed and is easy to infect, and especially has unsatisfactory effects on emergency hemostasis of some acute wounds and follow-up care of chronic wounds (such as superficial II-degree burns and scalds, diabetic feet, ulcers and bedsores). With the development of the times, as a novel medical material, the bioactive glass has good biocompatibility, and a large number of microporous channels are arranged inside the bioactive glass, so that the bioactive glass can facilitate the transmission of nutrient components, the adhesion of proteins and peptides in extracellular matrix and the acceleration of the generation speed of a hydrous silicic acid gel layer, and further can accelerate the wound healing speed, and is widely applied as a raw material of dressing. However, in practical application, the biocompatibility of the bioactive glass raw material directly used in the existing bioactive glass dressing is not good enough, and the practical application effect of the dressing is influenced, so that the applicant invented a preparation method of bioactive glass (patent application No. ZL 201610870495.2), and the compatibility and affinity with human bodies are improved and the anaphylaxis and rejection reaction are reduced by supplementing mild animal materials to the surface of the bioactive glass. And good economic benefit and social benefit are obtained. However, we have further studied the action mechanism of the product in order to further improve the use effect of the product. The reason why the bioactive glass is found to achieve a good healing effect is that when the bioactive glass enters human body fluid, hydroxyapatite substances are deposited on the surface in the environment of the body fluid. The hydroxyapatite is an important raw material for forming the skeleton, can be chemically bonded with body tissues on an interface, has certain solubility in a body, can release ions harmless to the body, can participate in vivo metabolism, has stimulation or induction effect on hyperosteogeny, can promote the repair of defective tissues, and shows bioactivity, so the wound healing effect is closely related to the mineralization speed of the hydroxyapatite, the total mineralization time of the hydroxyapatite under normal conditions is about 21.5hrs, and the mineralization time is more than 1hr even if nano bioactive glass is used as a raw material. The difference of the mineralization time can cause slow speed of healing promotion and risk of spilling and losing the dressing or the newly generated mineralized substance by blood, and the functional dressing in the current market has no triple effects of imbibing, bacteriostasis and healing promotion, and has high material cost and price, thus influencing the practical application effect and batch popularization of the dressing.

Disclosure of Invention

The invention mainly solves the technical problem of providing a dressing which has the triple effects of absorbing liquid, inhibiting bacteria and promoting healing, thereby improving the speed and quality of acute wound healing and relieving the pain of patients.

In order to solve the technical problems, the invention adopts a technical scheme that: the high-affinity liquid dressing capable of being rapidly validated is provided, and the formulation of the high-affinity liquid dressing capable of being rapidly validated comprises the following components:

the balance of deionized water;

the compound bacteriostatic agent is

VEC or

One of VAC is plant extract bacteriostat and at least one of octenidine hydrochloride, polyhexamethylene biguanide and polyhexamethylene biguanide.

In a preferred embodiment of the present invention, the composite bacteriostatic agent in the composite bacteriostatic agent is

VEC or

The compounding ratio of the plant extraction bacteriostat of one VAC to at least one of octenidine hydrochloride, polyhexamethylene biguanide and polyhexamethylene biguanide is 12-20: 5 to 6.

In a preferred embodiment of the invention, the film-forming agent is one or more of polyvinyl alcohol, gellan gum and Pullulan (INCI Name: Pullulan).

In a preferred embodiment of the invention, the analgesic is one or two of borneol and menthol.

In a preferred embodiment of the present invention, a preparation method of the calcium and silicon ion bioactive buffer solution comprises:

firstly, selecting bioactive glass with calcium content of more than or equal to 12 percent, silicon content of more than or equal to 20 percent and phosphorus content of more than or equal to 1.5 percent, and carrying out surface animal affinity treatment on the bioactive glass to prepare animal affinity bioactive glass powder containing 1-30 nanometer micropores;

secondly, soaking the animal affinity bioactive glass powder in deionized water at the constant temperature of 80 ℃ for 72hrs, controlling the pH value to be 10.2-11.8, detecting the concentration of leached ions, and taking the leached ion concentration as a leaching end point when the concentration of the leached ions is more than or equal to 5000 ppm;

and thirdly, extracting the leaching solution, and then filtering the leaching solution through a microporous filter with the pore size of 0.45 micron to obtain the corresponding calcium and silicon ion bioactive buffer solution.

In a preferred embodiment of the present invention, another preparation method of the calcium and silicon ion bioactive buffer solution is as follows: firstly, selecting bioactive glass with calcium content of more than or equal to 12 percent, silicon content of more than or equal to 20 percent and phosphorus content of more than or equal to 1.5 percent, and carrying out surface animal affinity treatment on the bioactive glass to prepare animal affinity bioactive glass powder containing 1-30 nanometer micropores;

secondly, mixing the animal affinity bioactive glass with 5% potassium hydroxide aqueous solution according to the ratio of 5: 1-5, heating to 60 ℃ and carrying out ultrasonic treatment;

thirdly, immersing the animal affinity bioactive glass powder extracted at room temperature into calcium chloride with the concentration of 3mol/L, slowly stirring for 12hrs, and carrying out calcification modification;

fourthly, soaking the modified animal affinity bioactive glass powder in deionized water for 72hrs at constant temperature, controlling the pH value to be 9.1-14.1, detecting the concentration of leached ions, and taking the leaching end point when the concentration of the leached ions is more than or equal to 5000 ppm;

and fifthly, extracting the leaching solution, and then filtering the leaching solution through a microporous filter with the pore size of 0.45 micron to obtain the corresponding calcium and silicon ion bioactive buffer solution.

In a preferred embodiment of the present invention, the preparation scheme of the modified bioactive glass loaded molecular sieve is as follows:

thirdly, adding the molecular sieves into the mixed solution for continuous ultrasonic treatment for 6-24 hours in multiple batches, wherein the total addition amount of the molecular sieves is half of that of the animal affinity bioactive glass;

and fourthly, filtering the solution, ultrasonically cleaning the residual solid for at least 3 times by using deionized water, removing water and drying to obtain the modified molecular sieve loaded with the bioactive glass, wherein the drying temperature is 100 ℃, and the drying time is 2 hrs.

The molecular sieve is a zeolite molecular sieve, the specification of the molecular sieve is preferably 2-4um in particle size, the standard pore diameter is 0.3-1 nanometer, and the static water adsorption ratio is more than or equal to 20-30%. Wherein the preferred pore diameter is 0.3 nanometer, and the static water adsorption ratio is 25 percent of molecular sieve.

In a preferred embodiment of the invention, the humectant is medical glycerin and trehalose in a ratio of 5: 1-25 in proportion.

The invention has the beneficial effects that: the invention has good biological compatibility, can maintain an acid-base microenvironment required by wound healing and provide inorganic elements required by wound healing by forming a bacteriostatic protection layer on the surface of the wound, promotes the wound to heal quickly, realizes a quick hemostasis effect by using the high-calcium molecular sieve, and reduces scars. And the mineralization speed of the hydroxyapatite on the surface is shortened to 10-15 min, so that the method is particularly suitable for cooperative nursing after debridement of various acute wounds (such as puncture wound, crush wound, glass fragment wound, blunt contusion, operation incision and firearm wound) and chronic wounds (such as shallow II-degree burn and scald, diabetic foot, ulcer and bedsore), and can reduce the use amount of expensive bioactive glass materials in dressing, further reduce the production cost and further contribute to realizing higher drug consumption ratio. The finished products which can be made by the invention include but are not limited to the functional dressing with the mechanical letter and the disinfection article with the letter-eliminating letter.

Drawings

FIG. 1 is a schematic diagram of the mineralization principle of hydroxyapatite in a bioactive glass artificial body fluid;

FIG. 2 is an FT-IR spectrum of hydroxyapatite after mineralization in an artificial body fluid;

FIG. 3 is a 72hrs leach IR profile in buffer.

Detailed Description

The following detailed description of the preferred embodiments of the present invention, taken in conjunction with the accompanying drawings, will make the advantages and features of the invention easier to understand by those skilled in the art, and thus will clearly and clearly define the scope of the invention.

Referring to fig. 1 to 3, an embodiment of the present invention includes:

example 1

A fast-acting high-affinity liquid dressing comprising the following components in the formulation:

the balance of deionized water.

The composite bacteriostatic agent in the composite bacteriostatic agent is a plant extraction bacteriostatic agent

VEC and octenidine hydrochloride were mixed according to 20: 5, and compounding the components in a ratio.

The preparation method of the calcium and silicon ion bioactive buffer solution in the embodiment is as follows:

The preparation scheme of the modified bioactive glass loaded molecular sieve in the example is as follows:

thirdly, measuring a zeolite molecular sieve with half mass of the animal affinity bioactive glass powder, adding the molecular sieve into the mixed solution for continuous ultrasonic treatment for 6-24 hrs in multiple batches, wherein the specification of the zeolite molecular sieve is 2-4um in particle size, 0.3-1 nm in standard pore size, the static water adsorption ratio is more than or equal to 20-30%, and preferably adding a product with 0.3 nm in pore size and 25% in static adsorption ratio;

Example 2

the balance of deionized water.

VAC with octenidine hydrochloride and polyhexamethylene biguanide as 12: 5: 1 is prepared by compounding according to the proportion of 1.

thirdly, immersing the animal affinity bioactive glass powder extracted at room temperature into calcium chloride with 3mol concentration, slowly stirring for 12 hours, and carrying out calcification modification, wherein the stirring mode is magnetic stirring, the magnetic stirring speed is 800-1000 r/s, the reason for carrying out calcification modification by stirring and soaking is that the microstructure framework of the bioactive glass is a tetrahedral framework structure based on Si atoms, the Si atoms are quadrivalent, chemical bonds of the Si atoms are respectively connected with sodium, potassium and oxygen atoms, in order to further improve the generation of a hydroxyl-like phosphate structure during leaching in the bioactive glass and improve the concentration of calcium elements in molecules, calcification treatment is carried out in advance, sodium and potassium in the molecules are replaced by calcium elements, and the ion replacement process is a chemical equilibrium process, so a certain temperature is required to promote ion activation, and the solution has certain movement, the motion speed cannot be too high, and the balance direction is influenced, so that only low-speed stirring or magnetic stirring is adopted;

fourthly, soaking the modified animal affinity bioactive glass powder in deionized water at constant temperature for 72 hours, controlling the pH value to be 9.1-14.1, detecting the concentration of leached ions, and taking the leached ion concentration as a leaching end point when the concentration of the leached ions is more than or equal to 5000 ppm;

In the above two embodiments, those manufactured by the Guangzhou Ezepine Biotechnology Ltd

VEC and

VAC plant extract bacteriostatic agent

VEC comprises cortex Cinnamomi extract, flos Caryophylli bud extract, herba Artemisiae Scopariae extract, cortex Magnolia officinalis bark extract, radix Sophorae Flavescentis extract, semen glycines extract active substance, 1, 2-hexanediol, and butanediol.

VEC comprises peony root bark extract, herba Artemisiae Scopariae extract, cortex Cinnamomi extract, flos Caryophylli bud extract, Galla chinensis extract, 1, 2-hexanediol, and butanediol. On one hand, the plant extraction bacteriostatic agent can influence the cell membrane potential of thalli cells by influencing the permeability and the function of cell walls and cell membranes, so that the metabolism of bacteria is slowed down and finally the bacteria die; on the other hand, the energy metabolism and the material synthesis of the thalli and the synthesis of nucleic acid and protein can be influenced by interfering the related synthetase system in the thalli, the replication and the transcription of genetic materials are blocked, the synthesis of protein is interfered, the growth and the reproduction of the thalli are inhibited, and the death of microorganisms is caused. The antibacterial agent has the characteristics of mild synergistic anti-allergy, high-efficiency bacteriostasis and good compatibility, conforms to the development trend of bacteriostatic agents with broad-spectrum antibiosis, strong bacteriostasis, mildness, low irritation and natural green sources, and has good synergistic effect with new-generation environment-friendly antibacterial agents such as octenidine hydrochloride, polyhexamethylene biguanide and the like.

The buffer solutions in the examples 1 and 2 are prepared by leaching on the basis of the animal affinity bioactive glass patented by the applicant, and the buffer solution prepared in the way is semi-mineralized buffer solution, which is beneficial to improving the mineralization speed of the wound surface. The difference between the leaching method in example 1 and the leaching method in example 2 is that the proportion of calcium ions in the final buffer solution in the leaching 2 is higher, so that the later mineralization speed is relatively faster. The reason for using the animal affinity bioactive glass is that the bioactive glass has better compatibility with human skin after being treated by the tussah protein, and can reduce the anaphylactic reaction when the whole liquid dressing is contacted with the skin.

The reason why the animal affinity bioactive glass is used as the carrier of the zeolite molecular sieve in the embodiment is that although the zeolite molecular sieve has a good hemostatic effect, the zeolite molecular sieve can generate transient local high heat to cause discomfort when contacting wound blood, and the high heat burn and discomfort can be effectively reduced after the load is modified, so that the healing effect and the survival rate are improved.

The working principle of the invention is as follows:

the process of forming the hydroxyapatite-like structure is the mineralization process of bioactive glass, and is one of the main factors for promoting the healing of skin wounds rapidly when the bioactive glass is used as a dressing, when the common bioactive glass 45S5 is used as a dressing, the surface mineralization mechanism is shown in figure 1, the mineralization time in simulated artificial body fluid is basically about 21.5hrs, the FT-IR spectrogram after mineralization is shown in figure 2, the mineralization time is also generally about 1hrs even when the nano-scale bioactive glass is used, the ion leaching ratio in the buffer is basically the same as that in the bioactive glass in the application, the 72hrs leaching IR chart is shown in figure 3, as can be seen from the comparison of the peak shapes in figures 2 and 3, the hydroxyapatite-like structure in the buffer is already appeared, and compared with the mineralization process in body fluid of the conventional bioactive glass dressing, the bioactive glass is not contacted with the body fluid, and the condition mainly taking the ion form as the main condition is called semi-mineralization, because the condition is unstable, when the hydroxyapatite-like structure in the buffer solution contacts with body fluid, the hydroxyapatite-like structure with stable structure can be quickly reacted to produce hydroxyapatite-like structure which is deposited near the wound, namely the mineralization step is completed. The actual verification shows that the complete mineralization time is 10-15 minutes, the speed is far higher than that of the common mesoporous bioactive glass, and the mineralization speed is also obviously improved compared with that of the nano-organic bioactive glass. The rapid and complete mineralization has good effects on promoting acute wound healing, particularly healing wounds such as diabetic wounds, bedsores and the like, healing wounds in complex environments after cancer operations and healing wounds after infected operations, specific data are shown in tables 5-8, and the overall healing time can be obviously shortened according to the data. On the basis, the liquid absorption and hemostasis capabilities are enhanced by adopting the modified bioactive glass loaded molecular sieve, and the effect of quickly stopping bleeding of patients with acute traumatic bleeding is achieved, specific data are shown in table 9, and as can be seen from the table, the average hemostasis time of example 1 is about 26s, the shortest time is 17s, the longest time is 45s, the average hemostasis time of example 2 is about 24s, the shortest time is 15s, and the longest time is 35s, so that the hemostasis speed of example 2 is slightly higher, and the data range concentration is better.

The relevant detection data of the invention are as follows:

1. pesticide residue test analysis

TABLE 1 pesticide residue test Table

2. Acute oral toxicity test:

TABLE 2 test results of acute oral toxicity of test substances to mice

The detection basis is as follows: 2015 edition of cosmetic safety specifications;

the test method comprises the following steps: a) dosage: the formal test adopts a maximum test, and the test design shows that the dosage of the test substance is 5000mg/kg body weight; b) contamination: the test solution is administered by oral gavage according to the amount of 0.2ml/10g body weight, and the animals are fasted for 4h before gavage and freely drink water; c) and (4) observation: the test was observed for 14 days and symptoms of intoxication and death were recorded.

And (3) test results: all tested animals have no obvious toxic symptoms and death in the observation period, and the general anatomy of the experimental animals has no abnormality. Therefore, acute oral toxicity LD of mice₅₀>5000mg/kg of body weight belongs to actual nontoxic substances.

3. Acute transdermal toxicity test:

TABLE 3 test results of acute oral toxicity of test substances to mice

and (3) test results: all tested animals have no obvious toxic symptoms and death in the observation period, and the general anatomy of the experimental animals has no abnormality.

Acute percutaneous toxicity LD of mice₅₀>2500mg/kg body weight, which belongs to a micro-toxic substance.

4. Acute skin irritation test:

TABLE 4 acute skin irritation test of the test substances in rabbits

and (3) test results: no irritation of the rabbit skin by the test substance was observed at any of the observation points. 24. The highest integrated mean was 0 at each observation time point for 48 and 72 hours. The test substance has no irritation to rabbit acute skin irritation according to method skin irritation intensity grading standard.

5 general wound healing assay

Table 5: wound healing analysis table after treatment of test group subject and control group subject

Ps: example 1 reference is made to formula treatment data.

6. Diabetic wound healing assay

Table 6: wound healing analysis table after treatment of test group subject and control group subject

Ps: reference formula treatment data was used with example 2.

7. Lung cancer postoperative complex environment difficult healing analysis

Table 7: wound healing analysis table after treatment of test group subject and control group subject

Ps: reference formula treatment data was used with example 2.

8. Analysis of non-healing wounds after infected surgery.

Table 8: wound healing analysis table after treatment of test group subject and control group subject

Ps: reference formula treatment data was used with example 2.

9. And (3) rapid hemostasis test:

TABLE 9 quick hemostasis test table

Ps; all patients with acute wound bleeding include arterial and venous bleeding.

The statistical results show that the hemostasis speed of example 2 is slightly faster than that of example 1, and the data distribution concentration is better.

The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes performed by the present specification and drawings, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.

Claims

1. A high-affinity liquid dressing capable of being rapidly validated is characterized in that the formula of the high-affinity liquid dressing capable of being rapidly validated comprises the following components:

1.3 to 2.5 percent of composite bacteriostatic agent

0.2 to 1.5 percent of film-forming agent

0.02-0.1% of pain killer

8-10% of calcium and silicon ion bioactive buffer solution

0.5 to 20 percent of modified bioactive glass loaded molecular sieve

1.2 to 6 percent of humectant

0.2 to 1.5 percent of absolute ethyl alcohol

The balance of deionized water;

the compound bacteriostatic agent is one of NAGO VEC or NAGO VAC plant extraction bacteriostatic agent and octenidine hydrochloride, polyhexamethylene biguanide, at least one of poly biguanide is compounded to form.

2. The high affinity liquid dressing that can validate fast of claim 1, characterized in that, among the compound bacteriostat for NAGO VEC or NAGO VAC one of the plant extract bacteriostat and at least one of octenidine hydrochloride, polyhexamethylene biguanide, poly biguanide the compounding proportion of 12~ 20: 5 to 6.

3. The fast-acting, high-affinity liquid dressing according to claim 1, wherein said film-forming agent is one or more of polyvinyl alcohol, gellan gum, and Pullulan (INCI Name: Pullulan).

4. The rapidly acting, high affinity liquid dressing of claim 1,

the analgesic is one or two of Borneolum Syntheticum and Mentholum.

5. The fast acting high affinity liquid dressing of claim 1, wherein said calcium and silicon bioactive buffers are prepared by a method comprising:

6. The fast acting high affinity liquid dressing of claim 1, wherein said calcium and silicon bioactive buffers are prepared by a method comprising:

thirdly, immersing the animal affinity bioactive glass powder extracted at room temperature into calcium chloride with the concentration of 3mol/L, and slowly stirring for 12Hrs, and carrying out calcification modification;

fourthly, soaking the modified animal affinity bioactive glass powder in deionized water at constant temperature for 72Hrs, controlling the pH value to be 9.1-14.1, detecting the concentration of leached ions, and taking the leached ion concentration as a leaching end point when the concentration of the leached ions is more than or equal to 5000 ppm;

7. The rapidly acting high affinity liquid dressing according to claim 1, wherein the modified bioactive glass loaded molecular sieve is prepared according to the following scheme:

thirdly, adding the molecular sieves into the mixed solution for continuous ultrasonic treatment for 6-24 hrs in multiple batches, wherein the total addition amount of the molecular sieves is half of that of the animal affinity bioactive glass;

and fourthly, filtering the solution, ultrasonically cleaning the residual solid for at least 3 times by using deionized water, dewatering and drying to obtain the modified molecular sieve loaded with the bioactive glass, wherein the drying temperature is 100 ℃, and the drying time is 2-3 hrs.

8. The dressing of claim 7, wherein the molecular sieve is a zeolite molecular sieve having a particle size of 2-4um and a standard pore size of 0.3-1 nm, and the static water adsorption ratio is greater than or equal to 20-30%.

9. The rapidly acting high affinity liquid dressing according to claim 7, wherein the molecular sieve has a pore size of 0.3 nm and the static water adsorption fraction is 25%.

10. The rapidly acting, high affinity liquid dressing of claim 1 wherein said humectant is medical glycerin and trehalose in a ratio of 5: 1-25 in proportion.