• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Method of preparing a formulation of topical application, rich in platelets and growth factors, in which a supernatant obtained from a platelet-rich plasma obtained from a subject is mixed with a polymerized protein composition, also obtained from a plasma rich in platelets from the same subject, obtaining an autologous formulation, with regenerative properties, and with a consistency of cream or "serum" without the need to add additives, preservatives, dyes or other excipients. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2633815A1
    申请号:ES201630355
    申请日:2016-03-23
    公开日:2017-09-25
    发明作者:Eduardo Anitua Aldecoa
    申请人:BTI Biotechnology Insttitute；
    IPC主号:
    专利说明:

    FORMULATION OF TOPICAL APPLICATION, RICH IN PLATES AND / OR GROWTH FACTORS AND A METHOD OF PREPARATION OF THE SAME

    DESCRIPTION 5

    Technical sector

    The invention relates to a topical application formulation, rich in platelets and / or growth factors, comprising a mixture of a supernatant obtained from a platelet rich plasma from a subject with a polymerized protein composition, also obtained from a platelet rich plasma from the same subject. The invention also relates to a method of preparing said formulation. fifteen

    State of the art

    In the field of medicine and dentistry, the use of compositions prepared from blood, which have 20 tissue regenerating properties, such as bone tissue, is known.

    In particular, the preparation of platelet rich plasma (PRP) from the blood of a patient is known. For the preparation of platelet-rich plasma, an initial amount of blood is started, which is processed, usually by centrifugation, to separate blood into fractions, including a fraction of red blood cells and a fraction of platelet-rich plasma. Next, all or part of the plasma fraction is separated and said separate part is used for different medical applications. 30

    An example of platelet rich plasma is known as growth factor rich plasma (PRGF). To obtain PRGF, a patient's blood is centrifuged for example at 580g for 8 minutes, obtaining a lower fraction of red blood cells, an intermediate fraction of white blood cells or leukocyte layer and an upper fraction of plasma. This upper plasma fraction has a platelet concentration gradient throughout the entire fraction, the concentration in the lower part of the plasma fraction being greater, closer to the white blood cell fraction. Then, all or part of the plasma fraction is removed and further processing is performed. Depending on the part extracted and processed, different formulations or compositions are obtained.

    For example, at least 50% of the volume of plasma adjacent to the leukocyte layer, which is the part of the platelet-rich plasma 10, can be extracted. Then, calcium chloride (CaCl2) is added to the extracted plasma, to initiate plasma coagulation and the release of growth factors. At that time, there is therefore a still liquid formulation rich in growth factors, which can be used immediately for applications that require a plasma rich in growth factors of liquid consistency. Examples of such applications are maintaining grafts, infiltrations, surface wetting, etc. In dermatology and aesthetic medicine applications, this liquid formulation is infiltrated intradermally to enhance the regenerative capacity of the skin. twenty

    In another example, at least 50% of the volume of plasma located immediately above the leukocyte layer is extracted and once extracted the plasma is activated with calcium chloride (CaCl2), initiating the coagulation of the plasma and the release of growth factors. Instead of using the plasma immediately, it is expected at a time of at least 15 minutes. During this time, the calcium ions progressively activate the platelets present in the plasma and the plasma thrombin is transforming the fibrinogen present in thin strands of fibrin that are intertwined with each other. After this period, a three-dimensional fibrin matrix with numerous domains of growth factor binding is obtained, which makes it an ideal controlled release system. The growth factors that were previously inside the platelets are thus gradually released following a sustained release kinetics, that is, a gradual kinetics whereby instead of releasing all the factors at the same time they are doing so. progressively over time. This three-dimensional matrix or clot is usually used, for example, for the closure of chronic wounds such as venous type ulcers.

    In yet another example, an upper part of the plasma fraction, less rich in platelets, is extracted. Calcium chloride (CaCl2) is added to initiate plasma coagulation. The coagulation process is allowed to end and then the clot retracts, obtaining a three-dimensional fibrin membrane ("three-dimensional fibrin membrane") and a liquid known as a supernatant. Coagulation 10 and retraction usually require an approximate time of 45 to 60 minutes. The fibrin membrane has more consistent biomechanical properties than the aforementioned clot; in particular, it resists a greater compression force and keeps the volume more permanent and durable compared to the clot. In addition, the fibrin membrane can be used as a support or biological scaffold with hemostatic properties. Support or scaffolding means a matrix that temporarily serves as a structure while a tissue is regenerating. Due to its ability to exert support, the membrane is suitable for some medical applications such as performing surgical sutures or sealing biological defects.

    In another example, all or part of the plasma fraction is removed, calcium chloride (CaCl2) is added and approximately 60 minutes are allowed to ensure that plasma coagulation and clot retraction occurs, forming a membrane of fibrin and a supernatant with the particularity that the majority of growth factors and proteins initially contained in the fibrin clot have passed to the supernatant. Then, the supernatant is separated for use in applications such as research trials, for example as a culture supplement for in vitro studies with dermal fibroblasts. The use of the supernatant as eye drops is also known.

    That is, as can be seen, this versatile technology of plasma rich in growth factors has evolved around multiple medical areas, being very advantageous because it is completely autologous in addition to presenting useful biological effects. The regenerative capacity of the protein complex present in the plasma rich in growth factors has proven to be very effective in disciplines as diverse as ophthalmology, neurobiology, traumatology and dermatology. However, each medical branch requires particular application and dosage systems. For this reason, the search for new formulations based on plasma rich in growth factors is key to adapt and optimize the application of this technology to each pathology. 10

    For example, at present, despite the wide range of technical possibilities, it is considered that there is no galenic formulation that has a cream consistency that allows to apply the growth-rich plasma topically with success.

    Thus, there are certain compounds based on platelet-rich plasma that have a cream consistency and can be applied topically. However, these formulations 20 are based on mixing platelet rich plasma (not activated or activated) with some commercial cream base and with usual topical excipients. This fact makes the cream not autologous, since the commercial cream base and the excipients do not come from the patient's own blood. In addition, no biocompatibility studies have been carried out in this regard and the necessary knowledge is lacking to know if these commercial bases affect the integrity of the protein set provided by the patients. Another disadvantage of these existing creamy compounds is that, to prepare them, the patient's blood has to be transferred to a laboratory where the mixing and preparation of the creamy compound is performed, and then the compound has to be sent to the patient. This entails an additional cost and time to carry out said transports and a possible temporary storage of the compound.
     35
    The present invention aims to achieve a cream based on plasma rich in growth factors, wherein said cream or its method of preparation solve at least one of the above problems.

    Brief Description of the Invention 5

    The subject of the invention is a topical application formulation, comprising a supernatant obtained from a platelet-rich plasma from a subject, and further comprising a polymerized protein composition obtained from the same subject. The formulation 10 has a more or less dense cream consistency, depending on the proportion between the supernatant and the polymerized protein composition.

    Likewise, a method of preparing a topical application formulation, in which a supernatant obtained from a platelet-rich plasma from a subject with a polymerized protein composition, also obtained from a rich plasma, is object of the invention in platelets from the same subject. Thus, the method initially has a first amount of blood from a subject. Said first quantity is separated into fractions for example by centrifugation, said fractions including a fraction of red blood cells and a fraction of platelet rich plasma. Then, an amount of platelet-rich plasma equal to all or part of the platelet-rich plasma fraction is extracted. The extracted amount is heated at a temperature between 60 and 100 ° C for at least 1 minute, and subsequently cooled for at least 1 minute, obtaining a composition with polymerized or gelled proteins, the composition having a semi-solid consistency. On the other hand, a second amount of blood is available from the subject. Said second quantity of blood is separated into fractions, for example by centrifugation, said fractions including a fraction of red blood cells and a fraction of platelet-rich plasma. All or part of the platelet-rich plasma fraction obtained from the second quantity of blood is extracted, and coagulation of said extracted quantity is allowed, obtaining a clot. Then, clot retraction is allowed to obtain a supernatant. Finally, the supernatant is mixed or combined with the composition with polymerized proteins, obtaining an autologous formulation with regenerative properties, and suitable for topical application in the subject. The formulation may have a more solid (cream) or more liquid consistency (serum or "serum") depending on the proportion of the mixture of supernatant and composition with polymerized proteins.

    In contrast to conventional formulations, the formulation obtained by the method according to the invention has a cream or "serum" type texture that makes it ideal for its superficial skin extension. Therefore, the method allows a new way to apply the autologous growth factors present in a platelet-rich plasma and / or growth factors such as PRGF, so that they can be absorbed through the skin without the need to inject them invasive way. A new biomaterial is achieved that can be used on large surfaces damaged by either burns or other skin conditions.

    The formulation obtained is also advantageous in that it is free of additives, preservatives, colorants or any other excipient. In addition, the formulation is one hundred percent autologous, and therefore constitutes a totally safe and biocompatible product for the subject in which it is to be applied. The creamy base that is used to create this biomaterial comes from the plasma fraction of the subject itself, so mixing with any type of external topical base is not necessary. 25

    In addition, the method of preparation of the formulation can be performed in situ, in the dermatological center itself where the patient comes to request treatment, the preparation time being relatively short (approximately 1.5 hours). 30

    An additional advantage of the formulation obtained is that it can be dosed and frozen for prolonged maintenance, without its microstructure or bioactivity being compromised.
     35
    In addition, high levels of growth factors have been detected in extracts of this formulation and it has been observed how the bioactivity of dermal fibroblasts cultured therewith increases significantly with respect to the absence of stimulation, that is, not adding the formulation according to the invention. . Bioactivity means the stimulation of cell proliferation, cell migration, etc. 5

    Brief description of the figures

    The details of the invention can be seen in the accompanying figures, not intended to be limiting the scope of the invention:

    - Figure 1 shows a graph of the growth factor content of the formulation according to the invention, calculated from six samples of different formulations. fifteen
    - Figure 2 shows illustrative graphs of the release kinetics of the growth factors PDGF-AB, EGF, IGF-I and TGF-β1 contained in the formulation according to the invention.
    - Figure 3 shows a graph of the cell proliferation of skin fibroblasts in a culture with a formulation according to the invention.
    - Figure 4 shows an illustrative graph of the synthesis of hyaluronic acid by human skin fibroblasts over time and by action of the formulation according to the invention. 25
    - Figure 5 shows an illustrative graph of the synthesis of type I collagen by human skin fibroblasts, by effect of the application of the formulation according to the invention.

    DETAILED DESCRIPTION OF THE INVENTION

    The object of the present invention is, on the one hand, a topical application formulation with a more or less dense cream consistency, comprising growth factors of platelet origin released and which is completely autologous. The formulation is based on the mixture of a blood plasma supernatant and a blood plasma protein gel. Both the supernatant and the gel are prepared from blood plasma from the same subject, who is in turn the preferred recipient of said topical formulation. The protein gel comprises proteins in a gelled state, such as albumin, glycoproteins, globulins and / or fibrinogen. 5

    The present invention also has as its object a method of preparing a topical application formulation, ideal for the treatment of skin problems or defects.
     10
    According to said method of preparation, blood is obtained from a human or animal subject or patient. Blood may be disposed in one or more containers or tubes. Next, the blood is separated into fractions, including a fraction of red blood cells and a fraction of platelet-rich plasma. The separation into fractions can be carried out for example by centrifuging the container or the containers at a speed of between 100 and 900 G for 3 to 12 minutes and at room temperature or not (that is, at any temperature). Within these ranges and in an especially advantageous way, centrifugation can be carried out at a speed of between 300 and 800 G, for a time of between 5 and 9 20 minutes and at room temperature. These ranges of spin parameters allow to obtain a more defined separation of the different fractions.

    Once the blood is separated into fractions, a first quantity of platelet-rich plasma and a second quantity of platelet-rich plasma are extracted from the same container or from different containers (in the case of having more than one container). The first amount of platelet rich plasma and the second amount of platelet rich plasma are extracted to different recipient containers. For example, it is possible to start from an initial amount of blood between 63 and 72 ml, and obtain at least 24 ml of platelet-rich plasma, of which 15.5 ml is used as the first quantity of plasma and 8.5 ml remaining as the second quantity of plasma.
     35
    Then, on the one hand, the first amount of plasma is heated at a temperature between 60 and 100 ° C for at least 1 minute. Next, the first amount of platelet-rich plasma is cooled for at least 1 minute, preferably at room temperature (approximately 20 to 30 ° C), obtaining a composition that includes polymerized or gelled proteins as a result of heating and cooling. In certain embodiments, the heating is carried out more specifically at a temperature of 70 to 85 ° C, whereby an optimal polymerization of plasma proteins is achieved, which ultimately affects the biomechanical characteristics of the protein gel for subsequent emulsion or mixed. The polymerized or gelled proteins may include albumin, glycoproteins, globulins and / or fibrinogen. Optionally, a platelet activating agent can be applied to the first amount of plasma before heating it. In preferred embodiments, the platelet activating agent is or comprises calcium chloride (for example 10% calcium chloride). Alternatively or additionally, the platelet activating agent may be or comprise human or animal thrombin (eg bovine), an application of cold and heat, and / or an application of ultraviolet light. The platelet activating agent causes platelets of the first amount of platelet-rich plasma 20 to release growth factors contained therein.

    On the other hand, a platelet activating agent is applied to the second quantity of platelet rich plasma. In preferred embodiments, the platelet activating agent is or comprises calcium chloride (for example 10% calcium chloride). Alternatively or additionally, the platelet activating agent may be or comprise human or animal thrombin (eg bovine), an application of cold and heat, and / or an application of ultraviolet light. The platelet activating agent causes the platelets of the second quantity of plasma rich in 30 platelets to release growth factors contained therein. Then, sufficient time is allowed to allow coagulation of the second quantity of platelet-rich plasma, obtaining a clot. The clot retraction is then allowed to occur, obtaining a liquid or supernatant. 35

    Once the polymerized protein composition and the supernatant are prepared, both are mixed, obtaining a creamy consistency formulation suitable for topical application. Preferably, the mixing is carried out in a proportion of 1 part by volume of supernatant for between 1 and 4 parts by volume of composition with 5 gelled proteins, whereby a topical biomaterial of varying creamy consistency is achieved, being able to obtain more or less high viscosities. so that its application is for example, by topical extension or drip. In certain embodiments, the mixing is carried out in a proportion of 1 part by volume of supernatant by 10 between 1 and 2 parts by volume of composition with gelled proteins, whereby a topical biomaterial of creamy consistency with an ideal viscosity is achieved for topical application by surface extension. In some embodiments, mixing can be done by hand, for example by vigorously mixing through a syringe connector for 2 or more minutes. In other embodiments, a mixer can be used to perform the mixing. The mixing can be carried out, for example, with a mixing force of 0.5 to 30 kg / cm2 or up to 200 N.
     twenty
    That is, in summary, the invention consists in obtaining on the one hand a protein gel based on the polymerization of plasma proteins. This gel serves as an autologous base from which the topical formulation is prepared. On the other hand, the supernatant rich in growth factors released is prepared. This liquid supernatant is free of platelets and fibrin. It is composed of the set of growth factors and bioactive morphogens released after the coagulation cascade of the plasma rich in growth factors. Once the supernatant and the protein gel are available, both are combined in such a way that the result conforms to a semi-solid mass capable of being topically applicable and extending covering a large cutaneous surface. By varying the ratio between the protein gel and the supernatant, a more or less solid formulation is obtained.
     35
    It has been proven that the mixture of the supernatant with the protein gel makes it possible to achieve a substance with the optimum texture for topical application. On the other hand, the formulation is advantageous since certain proteins (for example albumin), present in the gelled state in the formulation, can promote percutaneous absorption of the growth factors present in the liquid portion (the supernatant), due to the 5 ability of these proteins to promote the absorption of some drugs and to serve as carriers of different active ingredients. Therefore, mixing the supernatant with the protein gel not only allows obtaining a creamy consistency formulation but also enhancing the biological effect of the growth factors 10 applied to the skin.

    The following describes some tests carried out in order to characterize the topical formulation and verify its bioactive properties. In these tests reference is made to the term "serum." Said term has to be understood as a generic name to refer to the formulation according to the invention, and not as an indication of the texture or degree of solidity thereof (unless the texture or density of the "serum" is expressly described. or formulation).
     twenty
    Essay 1

    In this first trial, the autologous growth factor content of the topical formulation was evaluated. For this, the content of six different formulations from six respective donors was analyzed. The formulations had previously been prepared from the patients' blood, as follows:

    Each patient had 99 ml of blood drawn in a number of 11 containers (blood collection tubes). Each tube of blood collection has a capacity for 9 ml of blood. The blood tubes were introduced into a centrifuge and centrifuged at 580 G at room temperature for 8 minutes to separate the blood into fractions comprising a fraction of red blood cells and a platelet-rich plasma fraction. From the 99 ml of centrifuged blood, the entire column of platelet rich plasma was extracted, dividing said column into a first amount of 15.5 ml of platelet rich plasma and a second quantity of 8.5 ml of plasma rich in platelets Then, the first amount of platelet-rich plasma was heated for 12 minutes at 79 ° C, and the first amount of platelet-rich plasma was allowed to cool to room temperature for 5 minutes to obtain a polymerized protein composition. On the other hand, 0.17 ml of calcium chloride was applied as a platelet activating agent to the second quantity of platelet rich plasma. Coagulation of said second quantity of platelet rich plasma was allowed, obtaining a clot. Then, retraction of clot 10 was allowed for 1 hour at 37 ° C to obtain a supernatant. The supernatant was mixed with the composition with polymerized proteins, by manual emulsion through a syringe connector for 2 minutes to obtain a topical application formulation.
     fifteen
    Being a formulation whose active ingredient is a pure platelet extract, the content of the following key growth factors in tissue regeneration processes was analyzed by ELISA technique: epidermal growth factor (EGF), insulin growth factor (IGF -I), platelet-derived growth factor (PDGF-20 AB) and transforming growth factor-β1 (TGF-β1). The six formulations were centrifuged at 14000 G for 15 minutes, and a liquid extract of each formulation was obtained. The content of the above growth factors in each of the liquid extracts was measured, obtaining the average concentration values indicated in Figure 1. The results show that the topical formulation ("serum") according to the invention because it has a high content in said growth factors, an advantage that adds to the advantageous fact that the growth factors of each formulation are entirely autologous to the corresponding patient. 30

    Essay 2

    In the second trial, a study of release kinetics of growth factors PDGF-AB, EGF, IGF-I and TGF-β1 over time was performed. For this, by means of a process like the one described in Test 1, three formulations of three different ones were obtained. The three formulations were then immersed in an extraction medium for 7 days. Samples were taken at different times, to quantify the release of the aforementioned growth factors. Samples were taken at 3 hours, 5 hours, 5 24 hours and 7 days. Once the different extracts were obtained, the degree of bioactive protein release by the formulation was quantified by ELISA technique. As can be seen in Figure 2, the growth factors are released gradually until reaching a peak at 24h, which is substantially maintained until 10 7 days.

    Essay 3

    Once the content of growth factors and the ability to gradually release these proteins were determined, the biological potential of the formulation on different cell lines of dermal fibroblasts was evaluated.

    First, the ability of the formulation to induce cell proliferation was tested. For this, by means of a process like the one described in Test 1, three formulations were obtained from three respective donors. Then, liquid extracts of said formulations were obtained by centrifugation at 14000 G for 15 minutes. Subsequently, 20% of said extracts were applied in a cell culture medium free of supplements and up to two lines of dermal fibroblasts were cultured. After maintaining the cell cultures for 72 hours with said treatment, a quantitative analysis was performed by the Cyquant fluorimetric technique to quantify the amount of DNA (and therefore the number of cells that had been able to proliferate in response to the treatment). As seen in Figure 3, treatment with the formulation extract ("serum") was able to induce the proliferation of dermal fibroblasts in a significantly superior way to those not treated (non-stimulation control). 35

    Subsequently, the ability of the formulation to induce the biosynthetic activity of cell cultures was analyzed. More specifically, it was studied whether the formulation was capable of causing the synthesis of hyaluronic acid and type I collagen by dermal fibroblasts (two of the most important structural proteins of skin tissue). For this, by means of a process like the one described in Test 1, three formulations were obtained from three respective donors. Then, the formulations were centrifuged at 14000 G for 15 minutes, obtaining liquid extracts of the formulations. A 20% treatment was prepared in cell culture medium and two 10 different lines of dermal fibroblasts were maintained for 3 and 7 days. Culture media extracted at both times were analyzed by ELISA technique to quantify the degree of hyaluronic acid synthesis. As can be seen in Figure 4, the formulation ("serum") is capable of inducing the synthesis of hyaluronic acid, these results being especially significant with respect to the non-stimulation control at 7 days.

    To quantify the production of type 1 collagen, he used the Western Blot protein analysis technique. The results of Figure 5 show 20 as at 7 days of treatment with the formulation ("serum"), dermal fibroblasts are capable of synthesizing new type 1 collagen in a significantly superior way to cells grown with non-stimulation control .
     25
    In view of the results obtained, it can be concluded that the formulation obtained from the patient's blood has a high content of growth factors that sustainably releases, thus exerting a clear bioactive effect both at the level of cell proliferation and synthesis of key components of the skin such as hyaluronic acid and type I collagen.
    权利要求:
    Claims (6)
    [1]

    1. Method of preparation of a topical application formulation, characterized in that it comprises the steps of:
     5
    a) obtain blood from a subject;
    b) separating the blood into fractions comprising a fraction of red blood cells and a fraction of platelet rich plasma;
    c) extracting a first quantity of platelet rich plasma and a second quantity of platelet rich plasma; 10
    d) heating the first quantity of platelet rich plasma at a temperature between 60 and 100 ° C for at least 1 minute;
    e) cooling the first quantity of platelet rich plasma for at least 1 minute, obtaining a composition with polymerized proteins; fifteen
    f) apply at least one platelet activating agent to the second quantity of platelet rich plasma;
    g) allow coagulation of said second quantity of platelet rich plasma, obtaining a clot;
    h) allow clot retraction by obtaining a supernatant;
    i) mixing the supernatant with the composition with polymerized proteins, obtaining a topical application formulation.
     25
    [2]
    2. Method according to claim 1, characterized in that the platelet activating agent comprises calcium chloride.

    [3]
    3. Method according to claim 1, characterized in that the platelet activating agent comprises at least one of thrombin, a cold and heat application, and ultraviolet light.

    [4]
    Method according to claim 1, characterized in that it comprises the step of applying at least one platelet activating agent to the first amount of platelet rich plasma after step c) and 35 before step d).

    [14]
    14. Formulation according to claim 13, characterized in that the proteins comprise at least one of albumin, glycoproteins, globulins and fibrinogen.

    [15]
    15. Formulation according to claim 13, characterized in that the proteins are in a gelled state by a heating and cooling treatment.
    类似技术:
    公开号 | 公开日 | 专利标题
    ES2668398T3|2018-05-17|Compositions and procedures for tissue filling and regeneration
    ES2613547T3|2017-05-24|Allogeneic microvascular tissue for soft tissue treatments
    ES2896338T3|2022-02-24|Platelet-rich fibrin serum fraction
    JP2015529687A5|2016-10-27|
    ES2639561T3|2017-10-27|Procedure for preparing a growth factor concentrate derived from human platelets
    CN103071191A|2013-05-01|Preparation method of autologous platelet-factor-rich plasma | preparation
    ES2755172T3|2020-04-21|Formulation of a blood composition rich in platelets and / or growth factors, with gelled proteins, and method of preparation thereof
    ES2633815B1|2018-07-06|FORMULATION OF TOPICAL APPLICATION, RICH IN PLATES AND / OR GROWTH FACTORS AND A METHOD OF PREPARATION OF THE SAME
    ES2369945A1|2011-12-09|Process for a growth factor containing composition from platelets
    US11000629B2|2021-05-11|Methods related to minimally polarized functional units
    RU2506946C1|2014-02-20|Technique of platelet-rich plasma lyophilisation with preserving tgf pdgf vegf factor viability
    RU2717448C1|2020-03-23|Method of producing thrombocyte-rich plasma and method for producing thrombo-fibbrin gel or clot with serum, containing growth factors from unstabilised venous blood
    EP3638266A1|2020-04-22|Implants, methods for making implants and methods of treating lipoatrophy defects therewith
    ES2221770A1|2005-01-01|Preparation of a tissue regeneration agent comprises employing growth factors and protein rich coagulated materials
    US20120087983A1|2012-04-12|Orthopedic application of encapsulated stem cells
    US20160213764A1|2016-07-28|Composite tissue cancer vaccine
    CN111528218A|2020-08-14|Protective agent for fat tissue freezing
    Vijayaraghavan et al.2014|Role of Autologous Platelet Rich Plasma | in Wound Healing.
    RU2664478C2|2018-08-17|Method for producing a culture growth supplement based on human platelet lysate
    US20200093726A1|2020-03-26|Compound additive having biological activation function, preparation method therefor and use thereof
    Aminkov et al.2016|Application of platelet rich plasma | in treating of a complicated postoperative wound in a cat: a clinical case
    TWI535446B|2016-06-01|Method of preparing growth-factor-platelet-rich fibrin and releasate
    TW201509425A|2015-03-16|Method of using blood to prepare pharmaceutical composition for repairing wound
    RU2578429C2|2016-03-27|Beauty mask for face
    JP2016079177A|2016-05-16|Composition which promotes growth of dermal papilla cell, method for manufacturing the same, and medicinal drug containing the composition
    同族专利:
    公开号 | 公开日
    ES2633815B1|2018-07-06|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US5599558A|1989-09-15|1997-02-04|Curative Technologies, Inc.|Selecting amounts of platelet releasate for efficacious treatment of tissue|
    WO2005065269A2|2003-12-29|2005-07-21|Am Biosolutions|Compositions and method for decreasing the appearance of skin wrinkles|
    WO2009087560A1|2008-01-07|2009-07-16|Gwo Rei Biomedical Technology Corporation|Clottable concentrate of platelet growth factors and preparation method thereof|
    WO2010007502A2|2008-07-18|2010-01-21|Fondazione Irccs "Ospedale Maggiore Policlinico Mangiagalli E Regina Elena"|Platelet fraction deriving from placental blood|
    WO2010064267A1|2008-12-05|2010-06-10|Universita' Degli Studi Di Pavia|Platelets lysate and bioadesive compositions thereof for the treatment of mucositis|
    WO2013076507A2|2011-11-23|2013-05-30|Cell Therapy Limited|Platelet lysate gel|
    WO2015031465A1|2013-08-27|2015-03-05|Cook General Biotechnology Llc|Bioactive compositions derivable from platelet concentrates, and methods for preparing and using same|WO2020136296A1|2018-12-28|2020-07-02|Biotechnology Institute, I Mas D, S.L.|Fluid-mixing apparatus and mixing method|
    WO2020165473A1|2019-02-11|2020-08-20|Biotechnology Institute, I Mas D, S.L.|Tissue formulation or adhesive obtained from a blood composition containing platelets, and method of preparing such formulation|
    法律状态:
    2018-07-06| FG2A| Definitive protection|Ref document number: 2633815 Country of ref document: ES Kind code of ref document: B1 Effective date: 20180706 |
    优先权:
    申请号 | 申请日 | 专利标题
    ES201630355A|ES2633815B1|2016-03-23|2016-03-23|FORMULATION OF TOPICAL APPLICATION, RICH IN PLATES AND / OR GROWTH FACTORS AND A METHOD OF PREPARATION OF THE SAME|ES201630355A| ES2633815B1|2016-03-23|2016-03-23|FORMULATION OF TOPICAL APPLICATION, RICH IN PLATES AND / OR GROWTH FACTORS AND A METHOD OF PREPARATION OF THE SAME|
    [返回顶部]