Chitosan-based hemostatic composition and application thereof

Abstract

The invention discloses a chitosan-based hemostatic composition and application, and relates to the technical field of hemostatic compositions.The composition is prepared from, by mass, 5%-10% of chitosan, 3%-7% of polyvinylpyrrolidone, 1%-2% of calcium silicate, 1%-2% of montmorillonite, 0.1%-0.5% of triethanolamine, 2%-3% of polyethylene glycol and 70%-90% of water. Chitosan and PVP are dissolved under the condition that the pH is smaller than 6.5, then triethanolamine is added to adjust the pH to be about 7.8, and an ionic bond cross-linked membrane is formed under the participation of calcium silicate and montmorillonite; the hemostatic membrane disclosed by the invention can be quickly formed on a wound surface, realizes long-time hemostasis and physical isolation, and has the capability of re-forming the membrane; wound blockage and secondary injury caused by frequent replacement and application can be effectively reduced, the infection rate is greatly reduced, and the wound healing time is shortened; the hemostatic gel can be widely applied to nursing and hemostasis of superficial skin wounds after epidermis operation.

Description

Technical Field

[0001] The present invention relates to the technical field of hemostatic compositions, in particular to a chitosan-based hemostatic composition and its application. Background Art

[0002] Currently, in the market for post-epidermal surgery (such as hair transplantation, skin booster injection), there is no good hemostatic method for the extensive bleeding points on the superficial skin. One reason is that the bleeding points are often accompanied by exudate, and traditional dressings do not adhere well, and the hemostatic gauze cannot completely fit; the other reason is that the pressing hemostasis damages the skin and cannot cover all bleeding points at the same time.

[0003] The commonly used method in the market is to spray a liquid on the skin surface through a spray. Although this method can act on bleeding points over a large area, the action time is short, a large amount is required, and after a large dose of action, it will block the wound, which will instead cause slow skin healing. Summary of the Invention

[0004] In view of the above existing problems, the present invention is proposed.

[0005] The present invention provides a chitosan-based hemostatic composition and its application to solve the problem that the current hemostatic methods mainly rely on pressing hemostasis or applying hemostatic gauze, which have poor effects, for the extensive bleeding points on the superficial skin after epidermal surgery.

[0006] To solve the above technical problems, the present invention provides the following technical solutions:

[0007] In a first aspect, an embodiment of the present invention provides a chitosan-based hemostatic composition, which includes the following components by mass percentage:

[0008] Chitosan 5-10%, polyvinylpyrrolidone PVP 3-7%, calcium silicate 1-2%, montmorillonite 1-2%, triethanolamine 0.1-0.5%, polyethylene glycol PEG 2-3%, water 70-90%.

[0009] As a preferred scheme of the chitosan-based hemostatic composition of the present invention, among them: the chitosan is low-molecular-weight chitosan, which can be dissolved by introducing carbon dioxide under the condition that the pH value is less than 6.5, so as to improve the solubility and stability of the composition and effectively reduce the blockage of the bleeding site.

[0010] As a preferred scheme of the chitosan-based hemostatic composition of the present invention, among them: the triethanolamine is used to adjust the pH value of the composition to about 7.8, so as to generate ionic bonds or complex crosslinks between chitosan, polyvinylpyrrolidone and calcium ions, and form a stable and re-formable film layer on the skin surface during use.

[0011] In a second aspect, an embodiment of the present invention further provides a method for preparing a hemostatic composition based on chitosan, comprising the following steps:

[0012] Step S1: Introduce carbon dioxide into water and adjust the pH to less than 6.5, and dissolve chitosan in the obtained solution;

[0013] Step S2: Add polyvinylpyrrolidone to the solution obtained in Step S1 and blend to obtain a blended solution;

[0014] Step S3: Add triethanolamine to the blended solution obtained in Step S2 and adjust the pH of the blended solution to about 7.8;

[0015] Step S4: Add calcium silicate and montmorillonite to the solution obtained in Step S3 and stir evenly;

[0016] Step S5: Coat the mixture obtained in Step S4 on the surface of a polylactic acid film substrate;

[0017] Step S6: Dry at 50°C for 24 hours to obtain a hemostatic composition film based on chitosan.

[0018] As a preferred embodiment of the method for preparing a hemostatic composition based on chitosan according to the present invention, in Step S2, the mass ratio of chitosan to polyvinylpyrrolidone is 1:1, and it can be adjusted according to application requirements to balance the hemostatic efficiency and mechanical properties of the film layer.

[0019] As a preferred embodiment of the method for preparing a hemostatic composition based on chitosan according to the present invention, in Step S4, the calcium silicate and montmorillonite are evenly dispersed in the system. On the one hand, the amount of calcium ions is reduced to prevent blockage of the bleeding wound, and on the other hand, the mechanical strength and adhesion of the film layer are enhanced.

[0020] In a third aspect, the present invention provides a hemostatic patch, which is prepared by coating the above-mentioned hemostatic composition based on chitosan on the surface of a medical substrate, and the substrate is a polylactic acid film, a PET film or other medical thin film materials.

[0021] As a preferred embodiment of the hemostatic patch according to the present invention, the film layer formed on the wound surface during use of the hemostatic patch has a semi-transparent characteristic, which is convenient for observing and evaluating the wound healing degree in real time.

[0022] In a fourth aspect, the present invention provides an application of a hemostatic composition based on chitosan in the hemostasis of superficial bleeding points after epidermal surgery. The hemostatic composition is the composition described in the first aspect, which can act on the bleeding surface in a large area, and can form a film again after the film layer is damaged without blocking the wound, reducing the retention of exudate.

[0023] As a preferred embodiment of the application of the chitosan-based hemostatic composition in the hemostasis of superficial bleeding points after epidermal surgery, wherein: the hemostatic composition is applied to the hemostasis of the skin after cosmetic surgery, after injection of skin boosters and other superficial epidermal wounds, and the hemostatic effect is enhanced and wound repair is promoted through ionic bond crosslinking, reducing the risk of postoperative infection.

[0024] The beneficial effects of the present invention are as follows: in the present invention, ionic bonds or complexes are formed among chitosan, polyvinylpyrrolidone PVP and calcium ions, and a film layer with certain elasticity and adhesion can be rapidly formed on the wound surface; when the film layer locally swells or dissolves under the condition of exudate and then dries with the evaporation of water, it can form a film again, continuously protecting the wound and preventing secondary bleeding; calcium silicate and montmorillonite with a fixed ratio are used, which can moderately release calcium ions and provide the strengthening effect of inorganic fillers, while avoiding excessive blockage of the bleeding wound caused by high calcium ion concentration, promoting the normal drainage of exudate and reducing the risk of secondary infection; the film layer provided by the present invention has good ductility and adhesion performance, can adapt to the curve of the skin surface, and the film layer is semi-transparent, which is beneficial to the observation of the postoperative wound and reduces the damage to the newly formed tissue caused by frequent dressing changes; the composition provided by the present invention can be prepared through the processes of dissolution, blending, coating and drying under normal temperature or low temperature conditions, is easy for industrial production and large-scale promotion, and can be flexibly applied to various medical substrates, such as polylactic acid films, PET films, etc.

[0025] The present invention not only achieves rapid and sustainable hemostatic effects, but also has significant advantages in inhibiting infection, promoting wound healing and convenient use, and can meet the high-standard requirements of the medical and beauty fields for the care of superficial epidermal wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can also obtain other drawings based on these drawings without creative efforts.

[0027] Figure 1 It is a schematic flow chart of a preparation method of a chitosan-based hemostatic composition in Example 1. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0028] In order to make the above objects, features and advantages of the present invention more obvious and understandable, the specific embodiments of the present invention will be described in detail below with reference to the drawings in the specification.

[0029] In the following description, numerous specific details are set forth to provide a thorough understanding of the present invention. However, the present invention may be practiced in other ways than those specifically described herein. Those skilled in the art can make similar extensions without departing from the spirit of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0030] Secondly, the so-called "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment that is mutually exclusive with other embodiments.

[0031] Example 1, referring to Figure 1 , is the first embodiment of the present invention. This embodiment provides a method for preparing a hemostatic composition based on chitosan, and the raw material ratio is as follows:

[0032] Chitosan (low molecular weight) 6 wt%, polyvinylpyrrolidone (PVP) 4 wt%, calcium silicate 1.5 wt%, montmorillonite 1.5 wt%, triethanolamine 0.3 wt%, polyethylene glycol (PEG) 2.5 wt%, and the rest is water;

[0033] The preparation steps include:

[0034] 1) Dissolve chitosan: Under normal temperature conditions, introduce carbon dioxide into a container containing deionized water and adjust the pH to about 6.0, then slowly add chitosan and stir continuously until it is completely dissolved;

[0035] 2) Add PVP: Add polyvinylpyrrolidone powder to the chitosan solution obtained in step 1), and continue stirring for 15 minutes to make the two fully mixed and uniform;

[0036] 3) Adjust the pH: Slowly dropwise add triethanolamine to adjust the pH of the blend solution to about 7.8, and continue stirring for 10 minutes to ensure uniform pH inside the solution;

[0037] 4) Add inorganic powders: Add calcium silicate and montmorillonite powders and stir for about 20 minutes until the solid particles are uniformly dispersed in the solution;

[0038] 5) Film formation and drying: Uniformly coat the above mixture on the surface of a polylactic acid film substrate and dry it at 50 °C for 24 hours to obtain an external hemostatic film.

[0039] After testing, the prepared hemostatic film can rapidly form a stable film layer after contacting with skin exudate, and has the ability to form a film again, significantly reducing the blockage of the bleeding wound surface. Moreover, the film layer is semi-transparent, which is convenient for observing the wound healing situation.

[0040] Example 2, the second example of the present invention, provides a preparation method of a chitosan-based hemostatic composition. The raw material ratio is as follows:

[0041] Chitosan (low molecular weight) 8 wt%, polyvinylpyrrolidone (PVP) 5 wt%, calcium silicate 1 wt%, montmorillonite 2 wt%, triethanolamine 0.4 wt%, polyethylene glycol (PEG) 2 wt%, and the rest is water;

[0042] The preparation steps include:

[0043] 1) Dissolve chitosan: Add chitosan to an aqueous carbon dioxide solution with a pH of 6.4 and dissolve it completely;

[0044] 2) Add PVP: Add PVP to the chitosan solution under continuous stirring and stir for 15 minutes to disperse it evenly;

[0045] 3) Adjust the pH: Add triethanolamine to adjust the pH to about 7.8;

[0046] 4) Add inorganic powders: Slowly sprinkle calcium silicate and montmorillonite into the solution together and continue to stir for 20 minutes;

[0047] 5) Film formation and drying: Apply the obtained solution evenly on a PET film and dry it at 50 °C for 24 hours to obtain the finished film.

[0048] The mechanical properties of the finished film are more flexible and can better meet the hemostatic requirements for wounds in micro-curved areas. Through testing, it is found that compared with the formula in Example 1, the slightly higher chitosan content and slightly lower calcium ion addition in this example help reduce the accumulation of skin exudate and enhance the adhesion of the film layer.

[0049] Example 3, the third example of the present invention, provides a preparation method of a chitosan-based hemostatic composition. The raw material ratio is as follows:

[0050] Chitosan (low molecular weight) 10 wt%, polyvinylpyrrolidone (PVP) 6 wt%, calcium silicate 1.5 wt%, montmorillonite 1 wt%, triethanolamine 0.5 wt%, polyethylene glycol (PEG) 3 wt%, and the rest is water;

[0051] The preparation steps include:

[0052] 1) Dissolve chitosan: First, add chitosan to an aqueous carbon dioxide solution with a pH of 6.2 and dissolve it completely;

[0053] 2) Add PVP: Add polyvinylpyrrolidone and stir for about 15 minutes;

[0054] 3) Adjust the pH: Add triethanolamine to adjust the pH of the solution to about 7.8;

[0055] 4) Add inorganic powder: successively add calcium silicate and montmorillonite, and maintain stirring for more than 15 minutes;

[0056] 5) Film formation and drying: uniformly coat the obtained mixture on a polylactic acid film or medical-grade non-woven fabric, and dry at 50 °C for 24 hours to obtain a hemostatic film or patch.

[0057] Chitosan with a higher film layer content has a higher crosslinking density when forming ionic bonds and complexing with calcium silicate and PVP, and the hemostasis speed is improved; the film layer formed after re-swelling still has a good protective and isolating effect on the wound surface, which is beneficial to the observation and nursing during the wound healing process.

[0058] Experimental Example 1: To verify the application effect of the chitosan-based hemostatic composition of the present invention in the hemostasis of superficial skin wounds and subsequent healing process, compare with a conventional control group and a commercially available dressing, and evaluate the effects of the present invention in terms of hemostasis speed, infection risk, healing time, etc. The experimental protocol includes:

[0059] 1. Experimental animals

[0060] Select healthy SD rats (6 - 8 weeks old, body weight about 200 - 220 g), randomly divide them into groups, with 6 rats in each group.

[0061] 2. Group setting

[0062] Blank control group (Group A): Do not use any hemostatic material, only clean and expose the wound.

[0063] Conventional chitosan dressing group (Group B): Use a commercially available chitosan dressing, and the dosage and application method are carried out according to the product instructions.

[0064] Hemostatic patch group of Example 2 (Group C): Use the hemostatic film material described in Example 2 of the present invention to make a patch and apply it to the wound surface.

[0065] Hemostatic patch group of Example 3 (Group D): Use the hemostatic film material described in Example 3 of the present invention to make a patch and apply it to the wound surface.

[0066] 3. Modeling method

[0067] After anesthesia, divide the two sides of the rat's back into areas, and use a surgical blade to prepare superficial epidermal wounds (about 1 cm in length, depth not exceeding the dermis layer), avoiding damage to large blood vessels;

[0068] Prepare two wounds on the left and right sides of each rat's back;

[0069] After the wounds are prepared, apply the corresponding hemostatic materials according to the grouping arrangement.

[0070] 4. Observation indicators

[0071] Hemostasis time (s): The time from the appearance of bleeding at the wound until there is no obvious oozing or only a small amount of fluid exudation;

[0072] Infection rate (%): The proportion of animals showing obvious signs of infection such as redness, swelling, suppuration, and positive pus culture during the wound healing process;

[0073] Wound healing time (d): The average time for the wound to close, become completely dry, without redness or exudate;

[0074] Incidence of secondary bleeding (%): The probability of the wound bleeding again due to interference or dressing failure after initial hemostasis.

[0075] 5. Experimental procedure

[0076] Dressing use: In control group A, no treatment was given. In group B, a commercially available chitosan dressing was used. In groups C and D, the hemostatic patches prepared in Example 2 and Example 3 of the present invention were applied respectively;

[0077] Postoperative observation: Record the time taken for the wound to stop bleeding; Observe the wound condition daily thereafter, and count the infections and whether there is secondary bleeding;

[0078] Endpoint judgment: When the wound is completely dry, without redness and a normal epidermal tissue is formed, it is considered that the healing is complete.

[0079] Table 1 lists the results of the main observation indicators of each group of rats in this experiment (mean ± standard deviation).

[0080] Table 1:

[0081]

[0082]

[0083] The experiment shows that:

[0084] 1. In the blank control group (group A), due to no intervention with any hemostatic material, the average hemostasis time was relatively long (about 60 s);

[0085] The commercially available chitosan group (group B) significantly shortened the hemostasis time, but it was still significantly longer than those in Example 2 and Example 3 of the present invention;

[0086] The hemostasis times of the group of Example 2 (group C) and the group of Example 3 (group D) were both within 30 s, showing the characteristic of rapid hemostasis, which met the expectations of the present invention.

[0087] 2. The blank control group (group A) had no effective protective film coverage, and the infection rate was relatively high;

[0088] The commercially available chitosan group (Group B) reduced the infection rate to 6.7%, but there was still a certain probability of exudation and secondary infection;

[0089] No infection cases were observed in both the Example 2 group and the Example 3 group during the experimental period, indicating their good physical isolation and antibacterial properties.

[0090] 3. The average healing time of the blank control group exceeded 8 days;

[0091] The commercially available chitosan group was about 6 days;

[0092] Example 2 and Example 3 significantly shortened the healing process (both less than 5 days), indicating that the composition of the present invention can effectively maintain a dry and clean environment at the wound while stopping bleeding and reducing secondary injury, and promote epidermal repair.

[0093] 4. Secondary bleeding occurred in 13.3% and 6.7% of the blank control group and the commercially available chitosan group respectively;

[0094] No obvious secondary bleeding was observed in the Example 2 and Example 3 groups of the present invention, indicating that the formed ion cross-linked membrane layer can still maintain structural stability during exudation or local friction, and can form a film again, thus preventing rebleeding.

[0095] In summary,

[0096] After the composition of the present invention is applied to the wound surface, by means of the ionic bond / complexation of chitosan, PVP and calcium ions, a dense and elastic film layer is rapidly formed on the skin surface, reducing wound bleeding and achieving initial hemostasis in a short time;

[0097] Since the low molecular weight chitosan in the film layer itself has certain antibacterial activity, and the film layer can provide physical isolation for the wound surface, both Example 2 and Example 3 in the experimental results showed an infection rate of 0, which was significantly better than the blank group and the simple chitosan material group;

[0098] The excellent film-forming property not only improves the hemostasis efficiency, but also greatly reduces the accumulation of exudate on the wound surface, and avoids secondary injury to the wound caused by frequent dressing changes, thus accelerating the skin repair speed;

[0099] When the film layer is damaged or partially dissolved, a secondary film can be formed on the wound surface after partial evaporation of water, continuously protecting the wound, preventing secondary bleeding and external contamination, which fully reflects this advantage in animal experiments.

[0100] It can be seen from the comparison of the above experimental examples that the chitosan-based hemostatic composition of the present invention has excellent effects in rapidly stopping superficial skin bleeding, preventing infection and promoting wound healing, and is significantly superior to the blank control group and conventional commercially available chitosan dressings. In particular, its property of forming a film again in an exudate environment further reduces the secondary damage to the skin caused by frequent dressing changes, meeting the clinical requirements for rapid and gentle hemostasis of extensive epidermal bleeding points.

[0101] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the claims of the present invention.

Claims

1. A chitosan-based hemostatic composition, characterized in that, By mass percentage, it comprises the following components: Chitosan 5-10%, polyvinylpyrrolidone PVP 3-7%, calcium silicate 1-2%, montmorillonite 1-2%, triethanolamine 0.1-0.5%, polyethylene glycol PEG 2-3%, water 70-90%.

2. The hemostatic composition based on chitosan according to claim 1, wherein: The chitosan is low molecular weight chitosan.

3. The chitosan-based hemostatic composition according to any one of claims 1 to 2, characterized in that, The triethanolamine is used to adjust the pH value of the composition to 7.

8.

4. A method for preparing a chitosan-based hemostatic composition, characterized in that, It comprises the following steps: Step S1, introducing carbon dioxide into water and adjusting the pH to less than 6.5, and dissolving chitosan in the obtained solution; Step S2, adding polyvinylpyrrolidone to the solution obtained in Step S1 and blending to obtain a blended solution; Step S3, adding triethanolamine to the blended solution obtained in Step S2 and adjusting the pH of the blended solution to 7.8; Step S4, adding calcium silicate and montmorillonite to the solution obtained in Step S3 and stirring evenly; Step S5, coating the mixture obtained in Step S4 on the surface of a polylactic acid film substrate; Step S6, drying at 50°C for 24 hours to obtain a chitosan-based hemostatic composition film.

5. The preparation method of the chitosan-based hemostatic composition according to claim 4, characterized in that, In Step S2, the mass ratio of chitosan to polyvinylpyrrolidone is 1:

1.

6. The preparation method of the chitosan-based hemostatic composition according to claim 4, wherein: In Step S4, the calcium silicate and montmorillonite are evenly dispersed in the system.

7. A hemostatic patch, characterized in that, The hemostatic patch is prepared by coating the chitosan-based hemostatic composition according to any one of claims 1-3 on the surface of a medical substrate, and the substrate is a polylactic acid film, a PET film or other medical thin film materials.

8. The hemostatic patch according to claim 7, characterized in that, The film layer formed on the wound surface when the hemostatic patch is used has a semi-transparent characteristic.

9. Use of a chitosan-based hemostatic composition for hemostasis of superficial bleeding points after epidermal surgery, characterized in that, The hemostatic composition is the composition according to any one of claims 1-3.

10. The application according to claim 9, characterized in that, The hemostatic composition is applied to hemostasis after skin beauty surgery, after hydrodermabrasion and other superficial epidermal wounds.

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