Application of composition of polyester particles and sodium hyaluronate in medical beauty injection filler

Abstract

The invention relates to a composition of polyester particles and sodium hyaluronate, which is prepared by the following steps: preparing PCL (Polycaprolactone) microspheres with the particle size of 20-50 microns by an emulsion method; hA is selected, and a PBS buffer solution is used for preparing an HA solution; repeatedly freezing and thawing in a refrigerator at-80 DEG C for 3 times to form micro-crosslinked HA gel; and mixing the microspheres and the micro-crosslinked HA gel according to a mass ratio of 25: 75. The invention provides a technology of taking the physically micro-crosslinked HA as a suspension carrier, so that the polyester particles or microspheres can be stably suspended in an HA solution system without a chemical crosslinking agent, and an injection product has better biocompatibility and safety. HA which does not contain a chemical cross-linking agent and polyester particles / microspheres are mixed to serve as a medical beauty filling system, and the problem of stable suspension of the polyester particles / microspheres in the HA is solved by performing physical micro-crosslinking on the HA.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to the application of a composition of polyester particles and sodium hyaluronate in medical aesthetic injection fillers. Background Art

[0002] With economic development, people are increasingly focused on their appearance. Scars and wrinkles caused by congenital deformities and aging are common problems encountered by medical aesthetics institutions. Currently, cosmetic fillers lack the ability to maintain their effects stably and over time. Tissue engineering technology is playing an increasingly important role in tissue repair and organ augmentation. Recently developed regenerative materials are widely used due to their long-term effectiveness.

[0003] Existing regeneration products usually use cellulose materials such as CMC (carboxymethyl cellulose) as thickeners to deliver polyester particles or microspheres into tissues for implantation. However, cellulose materials have poor biocompatibility, strong inflammatory reactions, and are prone to embolism after entering blood vessels, resulting in existing regeneration products often accompanied by more complications. In addition, oxidative degradation of cellulose materials will produce aldehydes, which have the risk of causing granulomas and nodules. Another solution uses chemically cross-linked HA as a carrier to achieve a suspension effect in a gel state, but the cross-linking agent residues of the cross-linked HA are prone to cause delayed hypersensitivity reactions. Based on this, the present invention provides an application of a composition of polyester particles and sodium hyaluronate in medical aesthetic injection fillers. Summary of the Invention

[0004] In view of the defects of the prior art, the purpose of the present invention is to provide a composition of polyester particles and sodium hyaluronate for use in medical aesthetic injection fillers to solve the problems raised in the above background technology.

[0005] The present invention solves the technical problem by adopting the following technical solutions:

[0006] The present invention provides a composition of polyester particles and sodium hyaluronate, and the preparation of the composition comprises the following steps:

[0007] (1) PCL microspheres were prepared by emulsion method with a particle size of 20 to 50 μm;

[0008] (2) Select HA and prepare HA solution with PBS buffer;

[0009] (3) Repeated freezing and thawing three times in a -40°C refrigerator to form a micro-cross-linked HA gel;

[0010] (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75;

[0011] (5) defoaming the mixture by centrifugation;

[0012] (6) Fill the material into a prefilled syringe.

[0013] Preferably, the molecular weight of the HA is in the range of 1500 kDA to 3500 kDA.

[0014] Preferably, the molecular weight of the HA is in the range of 2000 kDA to 2500 kDA.

[0015] Preferably, the HA concentration is 10 mg / mL to 30 mg / mL.

[0016] Preferably, the HA concentration is 14 mg / mL to 20 mg / mL.

[0017] Preferably, the microspheres are microsphere polyester particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared from materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 1 to 150 microns; preferably 20 to 50 microns.

[0018] Preferably, the microspheres, HA, and saline solution are mixed and defoamed before filling in a pre-filled dosage form; wherein the saline solution is physiological saline or PBS buffered salt, and the osmotic pressure of the product is adjusted to between 280 and 350 Osmol / L;

[0019] The microspheres, HA, and excipients are mixed and lyophilized to form a lyophilized powder. Preferably, the excipient is mannitol, at a concentration of 0% to 45%, to facilitate reconstitution of the product. Upon use, the product is reconstituted with either normal saline for injection or water for injection, preferably normal saline for injection.

[0020] The present invention also provides an application of a composition of polyester particles and sodium hyaluronate in medical aesthetic injection fillers.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] In the present invention, a technology using physically micro-crosslinked HA as a suspension carrier is proposed, so that polyester microparticles or microspheres can be stably suspended in a HA solution system without chemical crosslinking agents, making the injectable product have better biocompatibility and safety. A mixture of HA without chemical cross-linking agents and polyester microparticles / microspheres is used as a medical aesthetic filling system: physical micro-cross-linking of HA is performed to solve the problem of stable suspension of polyester microparticles / microspheres in HA; the path of physical micro-cross-linking includes: repeated freezing and thawing; selection of HA in a specific molecular weight range to enhance the stability and suspension effect of the HA solution; selection of microparticles / microspheres with a specific particle size distribution to ensure the stability of the filler suspension and the maintenance of the effect after implantation; PBS buffer salt / sodium chloride is used to regulate the osmotic pressure of the product to reduce the inflammatory response after implantation; the osmotic pressure of the product is regulated between 280 and 350 Mosm / kg by adjusting the concentration of PBS buffer salt / sodium chloride, thereby reducing the inflammatory response in the early stage of implantation, reducing the phagocytic effect of macrophages on the implant material and the degradation of the HA material, thereby enhancing the maintenance of the effect after implantation; this technology solves the technical difficulty of suspending polyester microparticles / microspheres in HA without cross-linking agents, and prepares an injectable filling product with an osmotic pressure similar to that of human cells, which has better biosafety than existing products. Specifically, this technology addresses the embolism issues associated with traditional implant fillers, the pain and swelling that occur early after injection, and the risk of granulomas after long-term implantation. By overcoming the technical challenges of suspending polyester microparticles / microspheres in HA without a crosslinker, this technology creates an injectable filler product with an osmotic pressure similar to that of human cells, offering improved biosafety compared to existing products. Specifically, this technology addresses the embolism issues associated with traditional implant fillers, the pain and swelling that occur early after injection, and the risk of granulomas after long-term implantation. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of the electron microscope of the present invention. DETAILED DESCRIPTION

[0024] The following is a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with specific embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0025] The core working principle of the present invention is:

[0026] HA is selected from a specific molecular weight range and physically micro-crosslinked

[0027] Molecular weight range: 1500kDA~3500kDA, preferably 2000kDA~2500kDA

[0028] Physical micro-crosslinking process: Freeze-thaw cycles: Freeze-thaw parameters

[0029] HA concentration: 10mg / mL~30mg / mL, preferably 14mg / mL~20mg / mL

[0030] Polyester particles / microspheres: particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, PGA, or particles or microspheres prepared by materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 1 to 150 microns, preferably 20 to 50 microns

[0031] Microsphere mass ratio: 5% to 60%, preferably 15% to 35%, and optimally 20% to 30%

[0032] Product dosage form

[0033] (1) Pre-filled dosage form in which polyester microspheres, HA, and saline solution are mixed and defoamed before filling

[0034] Wherein: the salt solution is physiological saline or PBS buffer salt, and the osmotic pressure of the product is adjusted to between 280 and 350 Osmol / L

[0035] Freeze-dried powder dosage form prepared by mixing polyester microparticles / microspheres, HA, and excipients and then freeze-drying

[0036] Among them: the excipient can be mannitol, with a content of 0% to 45%, which mainly plays the role of promoting the re-dissolution of the product and can be added

[0037] Among them: When using the product, reconstitute it with normal saline for injection or water for injection, preferably with normal saline for injection

[0038] The preparation of a composition of polyester particles and sodium hyaluronate in this embodiment includes the following steps:

[0039] (2) PCL microspheres were prepared by emulsion method with particle size ranging from 20 to 50 μm;

[0040] (2) Select HA and prepare HA solution with PBS buffer;

[0041] (3) Repeated freezing and thawing three times in a -80°C refrigerator to form a micro-cross-linked HA gel;

[0042] (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75;

[0043] (5) defoaming the mixture by centrifugation;

[0044] (6) Fill the material into a prefilled syringe.

[0045] The molecular weight range of HA in this example is 1500 kDA to 3500 kDA.

[0046] The molecular weight range of HA in this example is 2000 kDA to 2500 kDA.

[0047] The HA concentration in this example is 10 mg / mL to 30 mg / mL.

[0048] The HA concentration in this example is 14 mg / mL to 20 mg / mL.

[0049] The microspheres of this embodiment are microsphere polyester particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared by materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 1 to 150 microns; preferably 20 to 50 microns.

[0050] The microspheres, HA, and saline solution of this embodiment are mixed and defoamed before filling in a pre-filled dosage form; wherein the saline solution is physiological saline or PBS buffered salt, and the osmotic pressure of the product is adjusted to between 280 and 350 Osmol / L;

[0051] The microspheres, HA, and excipients are mixed and freeze-dried to prepare a freeze-dried powder dosage form.

[0052] The excipient in this embodiment is mannitol, with a content of 0% to 45%, which is used to promote the reconstitution of the product; when the product is used, it is reconstituted with normal saline for injection or water for injection, preferably normal saline for injection.

[0053] This embodiment provides an application of a composition of polyester microparticles and sodium hyaluronate in medical aesthetic injection fillers.

[0054] Example 1

[0055] The preparation of a composition of polyester particles and sodium hyaluronate in this embodiment includes the following steps:

[0056] (3) PCL microspheres were prepared by emulsion method with a particle size of 20 μm;

[0057] (2) Select HA and prepare HA solution with PBS buffer;

[0058] (3) Repeated freezing and thawing three times in a -80°C refrigerator to form a micro-cross-linked HA gel;

[0059] (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75;

[0060] (5) defoaming the mixture by centrifugation;

[0061] (6) Fill the material into a prefilled syringe.

[0062] The molecular weight range of HA in this example is 1000 kDA.

[0063] The HA concentration in this example is 10 mg / mL.

[0064] The microspheres of this embodiment are microsphere polyester particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared by materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 1 micron; preferably 20 to 50 microns.

[0065] The microspheres, HA, and saline solution of this embodiment are mixed and defoamed before filling in a pre-filled dosage form; wherein: the saline solution is normal saline, and the osmotic pressure of the product is adjusted to 280Osmol / L;

[0066] This embodiment provides an application of a composition of polyester microparticles and sodium hyaluronate in medical aesthetic injection fillers.

[0067] Example 2

[0068] The preparation of a composition of polyester particles and sodium hyaluronate in this embodiment includes the following steps:

[0069] (4) PCL microspheres were prepared by emulsion method with a particle size of 50 μm;

[0070] (2) Select HA and prepare HA solution with PBS buffer;

[0071] (3) Repeated freezing and thawing three times in a -80°C refrigerator to form a micro-cross-linked HA gel;

[0072] (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75;

[0073] (5) defoaming the mixture by centrifugation;

[0074] (6) Fill the material into a prefilled syringe.

[0075] The molecular weight range of HA in this example is 3500 kDA.

[0076] The HA concentration in this example is 30 mg / mL.

[0077] The microspheres of this embodiment are microsphere polyester particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared by materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 1 to 150 microns; preferably 50 microns.

[0078] The microspheres, HA, and saline solution of this embodiment are mixed and defoamed before filling in a pre-filled dosage form; wherein the saline solution is physiological saline or PBS buffered salt, and the osmotic pressure of the product is adjusted to between 350Osmol / L;

[0079] This embodiment provides an application of a composition of polyester microparticles and sodium hyaluronate in medical aesthetic injection fillers.

[0080] Example 3

[0081] The preparation of a composition of polyester particles and sodium hyaluronate in this embodiment includes the following steps:

[0082] (5) PCL microspheres were prepared by emulsion method with a particle size of 35 μm;

[0083] (2) Select HA and prepare HA solution with PBS buffer;

[0084] (3) Repeated freezing and thawing three times in a -80°C refrigerator to form a micro-cross-linked HA gel;

[0085] (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75;

[0086] (5) defoaming the mixture by centrifugation;

[0087] (6) Fill the material into a prefilled syringe.

[0088] The molecular weight range of HA in this example is 2200 kDa.

[0089] The HA concentration in this example is 20 mg / mL.

[0090] The microspheres of this embodiment are microsphere polyester particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared by materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 25 microns; preferably 35 microns.

[0091] The microspheres, HA and saline solution of this embodiment are mixed and defoamed before being filled in a pre-filled dosage form; wherein the saline solution is physiological saline or PBS buffered saline.

[0092] This embodiment provides an application of a composition of polyester microparticles and sodium hyaluronate in medical aesthetic injection fillers.

[0093] Example 4

[0094] The preparation of a composition of polyester particles and sodium hyaluronate in this embodiment includes the following steps:

[0095] (1) PCL microspheres were prepared by emulsion method with a particle size of 25 μm;

[0096] (2) Select HA and prepare HA solution with PBS buffer;

[0097] (3) Repeated freezing and thawing three times in a -80°C refrigerator to form a micro-cross-linked HA gel;

[0098] (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75;

[0099] (5) defoaming the mixture by centrifugation;

[0100] (6) Fill the material into vials and freeze-dry.

[0101] The molecular weight range of HA in this example is 2000 kDA.

[0102] The HA concentration in this example is 19 mg / mL.

[0103] The microspheres of this embodiment are microsphere polyester particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared from materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 20 to 50 microns.

[0104] The excipient in this embodiment is mannitol, with a content of 20%, which is used to promote the reconstitution of the product; when the product is used, it is reconstituted with normal saline for injection or water for injection, preferably normal saline for injection.

[0105] Application of a composition of polyester microparticles and sodium hyaluronate in medical aesthetic injection fillers

[0106] The above is a detailed introduction to the application of a composition of polyester microparticles and sodium hyaluronate provided by this application in medical aesthetic injection fillers. Specific examples are used herein to illustrate the principles and implementation methods of this application. The description of the above embodiments is only used to help understand the method of this application and its core idea. At the same time, for those skilled in the art, based on the ideas of this application, other different forms of changes can be made on the basis of the above description. In summary, the content of this specification should not be understood as a limitation on this application.

Claims

1. A composition of polyester microparticles and sodium hyaluronate, characterized in that: The preparation of the composition comprises the following steps: (1) PCL microspheres were prepared by emulsion method with a particle size of 20 to 50 μm; (2) Select HA and prepare HA solution with PBS buffer; (3) Repeated freezing and thawing three times in a -80°C refrigerator to form a micro-cross-linked HA gel; (4) mixing the microspheres with the micro-cross-linked HA gel at a mass ratio of 25:75; (5) defoaming the mixture by centrifugation; (6) Fill the material into a prefilled syringe.

2. The composition of polyester microparticles and sodium hyaluronate according to claim 1, characterized in that: The molecular weight range of the HA is 1500 kDA to 3500 kDA.

3. The composition of polyester particles and sodium hyaluronate according to claim 2, characterized in that: The molecular weight range of the HA is 2000 kDA to 2500 kDA.

4. The composition of polyester particles and sodium hyaluronate according to claim 1, characterized in that: The HA concentration is 10 mg / mL to 30 mg / mL.

5. The composition of polyester particles and sodium hyaluronate according to claim 4, characterized in that: The HA concentration is 14 mg / mL to 20 mg / mL.

6. The composition of polyester particles and sodium hyaluronate according to claim 1, characterized in that: The microspheres are polyester microsphere particles, specifically particles or microspheres of homopolymers or copolymers of biodegradable polyester materials such as PCL, PLLA, PDLLA, PDDO, and PGA, or particles or microspheres prepared by materials end-capped or block-modified with small molecules such as PEG, with a particle size distribution of 1 to 150 microns; preferably 20 to 50 microns.

7. The composition of polyester particles and sodium hyaluronate according to claim 1, characterized in that: A pre-filled dosage form in which microspheres, HA, and saline solution are mixed and defoamed before filling; wherein the saline solution is physiological saline or PBS buffered salt, and the osmotic pressure of the product is adjusted to between 280 and 350 Osmol / L.

8. The composition of polyester particles and sodium hyaluronate according to claim 1, characterized in that: The microspheres, HA, and excipients are mixed and freeze-dried to prepare a freeze-dried powder dosage form.

9. The composition of polyester microparticles and sodium hyaluronate according to claim 8, characterized in that: The excipient is mannitol, with a content of 0% to 45%, which is used to promote the reconstitution of the product; when the product is used, it is reconstituted with normal saline for injection or water for injection, preferably normal saline for injection.

10. Use of the composition of polyester microparticles and sodium hyaluronate according to any one of claims 1 to 9 in medical aesthetic injection fillers.

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