WO2019079869A1 - Implant with reservoir containing sustained release micropores for subdermal application with thermoelastic and thermostatic properties and use of said implant - Google Patents

Implant with reservoir containing sustained release micropores for subdermal application with thermoelastic and thermostatic properties and use of said implant

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Publication number
WO2019079869A1
WO2019079869A1 PCT/BR2018/050161 BR2018050161W WO2019079869A1 WO 2019079869 A1 WO2019079869 A1 WO 2019079869A1 BR 2018050161 W BR2018050161 W BR 2018050161W WO 2019079869 A1 WO2019079869 A1 WO 2019079869A1
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WO
WIPO (PCT)
Prior art keywords
implant
thermoelastic
reservoir containing
micropores
subdermal
Prior art date
Application number
PCT/BR2018/050161
Other languages
French (fr)
Portuguese (pt)
Inventor
Rodrigo Otavio SARRAFF BERGER
Original Assignee
Sarraff Berger Rodrigo Otavio
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sarraff Berger Rodrigo Otavio filed Critical Sarraff Berger Rodrigo Otavio
Publication of WO2019079869A1 publication Critical patent/WO2019079869A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

  • the present invention pertains to the field of subdermal hormonal implants, more particularly the invention relates to a silicone reservoir, elastomer and silver nanoparticles on a 10 nm / ml scale of Polydimethylsiloxane (PDMS).
  • Said reservoir is in the form of a tube and has silicone with micropores which provide release of microspheres of the compound contained in said implant.
  • the present invention has for the purpose of providing a controlled release drug subdermal implant for the treatment of menstrual irregularities, premenstrual tension symptoms and pelvic pain, among other symptoms related to endometriosis.
  • This endoceptive is placed inside the uterus and, through a small reservoir, liberates slowly and progressively the levonogestrel salt, and should be replaced after the five year period.
  • patients report adverse effects such as breast tenderness, menstrual irregularity, bleeding-off and, in some cases, the onset of estrogen-producing cysts that need to be surgically removed.
  • the implant of the present invention was developed by using silicone polymers as the material so that it would not be bioabsorbable and could be removed at any time, in accordance with the patient's desire and medical recommendation.
  • silicone polymers this being preferably the polydimethylsiloxane, were added other components to promote reservoir advantages.
  • a blend was formed between the silicone polymer and an elastomeric polymer in order to promote greater flexibility to the implant, allowing prolonged release of the hormones contained therein.
  • the polymers used are resistant to temperature variation as a consequence of their chemical characteristics, and their functioning is not compromised by the variation in body temperature.
  • silver nanoparticles were added to the silicone chain in order to promote an anti-inflammatory and antimicrobial action, and several concentrations were tested until an ideal concentration that did not affect the properties of the polymer blend and the final material was found.
  • US3279996 discloses a thermoformed polysiloxane therapeutic implant designed for controlled release of medicaments for implantation into a target organ. This implant was designed for animal use, without major concerns with patient adaptation.
  • the controlled release subdermal implant of the invention taught herein is intended for use in humans, in addition to providing a better adaptation of the patients to the treatment, with advantages to the other methods already used.
  • a blend is used between the silicone polymer and an elastomer polymer, promoting greater flexibility to the implant, besides the insertion of silver nanoparticles, in order to guarantee an antimicrobial effect.
  • Patent US5756115 discloses a rectangular subdermal implant with a central core composed of a synthetic polymer base, such as polydimethylsiloxane, intermediate sides prepared from natural or synthetic polymeric materials such as cellulose and an outer layer prepared from natural or synthetic polymers allowing the diffusion of the medicament.
  • a synthetic polymer base such as polydimethylsiloxane
  • intermediate sides prepared from natural or synthetic polymeric materials such as cellulose
  • an outer layer prepared from natural or synthetic polymers allowing the diffusion of the medicament.
  • the controlled release subdermal implant of the present invention differs from this prior art implant because it is composed of a blend between the silicone polymer and an elastomeric polymer promoting greater flexibility to the implant.
  • the addition of silver nanoparticles also ensures an antimicrobial effect.
  • Patent document KR100445248A1 describes a polysiloxane-based compound containing at least one monovalent or bivalent metal as a grouping on the siloxane molecule, which may be copper, silver, zinc, magnesium, calcium or sodium metal.
  • the purpose of metal addition is to impart antimicrobial properties to the material.
  • the controlled release subdermal implant taught herein is composed of a blend between the silicone polymer and an elastomeric polymer, promoting greater flexibility to the implant.
  • the present invention teaches an implant with reservoir containing micropores of prolonged release for subdermic application with thermoelastic and thermostatic properties constituted by a blend polymer composition comprising a silicone polymer and an elastomer, with addition of silver ions in the range of 5 to 15 nm / ml incorporated into the silicone polymer chain, the addition of silver ions being preferably in the range of 10 nm / ml.
  • the silicone polymer of the present tube-shaped implant is preferably polydimethylsiloxane.
  • the implant with reservoir containing micropores of prolonged release for subdermal application has cylindrical format with height of 30 to 50 mm of height and of 1 to 3 mm of diameter, being the preferred height of the cylinder of 40 to 45 mm of height and 2 mm in diameter.
  • the outer surface of the implant is further coated with silanol (SiOH).
  • the invention further teaches a use of the implant in the hormonal treatment, preferably to treat endometriosis.
  • Figure 1 shows the implant with a micropore reservoir for extended release, this being a cylindrical silicone tube of preferred dimensions of 30 to 50 mm in height and 1 to 3 mm in diameter.
  • the silicone tube-shaped implant taught here has thermoelastic and thermostatic and thermostatic properties or thermosetting.
  • a linear polydimethylsiloxane, polydimethylsiloxane, inert, nontoxic and nonflammable polydimethylsiloxane organic polymer is used.
  • the present tube does not change its shape with high and low temperatures, due to its viscoelastic properties at high temperature.
  • the outer surface is coated with silanol (SiOH) so that, for a given time, there is a hydrophilic effect.
  • Implants in the form of tubes have intermediate hardness, with elasticity. The elasticity provides an increase in its diameter so that it can contain 140 to 160 mg of medicated salt.
  • Silicon tubes have nanoscale silver, which influences in approximately 10% of the functional biodynamics of the tube.
  • the tube is colorless and may have a slightly yellowish hue depending on the insertion of the silver.
  • the silicone elastomer implant has micropores to provide the release of microspheres of the salt to be used inside the tube.
  • the release, through micropores of the silicone, is done in a gradual and prolonged manner.
  • the reservoir in the form of a cylindrical tube needs to have elastic properties, being able to provide passage of the micronized salt through the micropores of the silicone.
  • the release will occur in a period between 6 to 12 months. That is, the present invention provides a subdermal implant which releases the medication in a constant and prolonged manner, with bactericidal action.
  • the invention is a silastic cylindrical tube for receiving a combination of usually subcutaneous application hormones.
  • the main purpose of the implant here taught is the more safe and efficient treatment of Endometriosis, in addition to the treatment of other associated pathologies.
  • the present silicone tube-shaped implant is suitable for high-temperature sterilization by gamma rays and is considered to be the best method of sterilization practiced in the area of medical devices.
  • the implant of the present invention has particularity, such as the placement of silver on the nanometer scale in the siloxane, with no compromising more than 10% of the biomechanics of the implant.
  • Silver on this scale has the effect of inhibiting local pro-inflammatory factors, it also has bactericidal effect.
  • the present invention provides less risk of encapsulation and implant rejection.
  • This reservoir of preferably 4.5cm will have thermoelastic property and will not suffer alteration in its functionality with the placement of up to 140 - 160mg of salts in its interior. The implants will be removed after 12 months.
  • the present invention thus teaches a reservoir implant containing long-release micropores for subdermal application with thermoelastic and thermostatic properties consisting of a polymer blend comprising a silicone polymer and an elastomer with addition of silver ions on the scale of 5 to 15nm / ml incorporated into the silicone polymer chain, the addition of silver ions being preferably in the range of 10nm / ml, wherein the silicone polymer of the present tube-shaped implant is preferably polydimethylsiloxane.
  • the present implant can be used for various non-hormonal medications for the prolonged release of medication in patients who need to receive oral medication on an ongoing basis. Therefore, the long-term treatments can be done in a more practical way, in addition to having its cost optimized.

Abstract

The present invention relates to the field of subdermal hormone implants and more specifically to a reservoir of silicone and elastomer with silver nanoparticles. More specifically, the invention relates to an implant with a reservoir containing sustained release micropores for subdermal application with thermoelastic and thermostatic properties comprising a polymer blend made up of a silicone polymer and an elastomer, with the addition of silver ions in the 5 to 15 nm/ml range incorporated into the polymer chain of the silicone, the addition of silver ions preferably being in the 10 nm/ml range.

Description

IMPLANTE COM RESERVATÓRIO CONTENDO MICROPOROS DE LIBERAÇÃO PROLONGADA PARA APLICAÇÃO SUBDÉRMICA COM PROPRIEDADES TERMOELÁSTICAS E TERMOSTÁTICA E USO DO DITO IMPLANTE  IMPLANT WITH RESERVOIR CONTAINING PROLONGED RELEASE MICROPORTS FOR SUBDERGER APPLICATION WITH THERMO-LATIC AND THERMOSTATIC PROPERTIES AND USE OF THE IMPLANT DIPLOMA
Campo de Invenção Field of Invention
[001] A presente invenção pertence ao campo dos implantes hormonais subdérmicos, mais particularmente a invenção trata de um reservatório de silicone, elastômero e nanopartículas de prata em escala de 10 nm/ml de Polidimetilsiloxano (PDMS). O referido reservatório tem a forma de um tubo e possui silicone com microporos que proporcionam liberação de microesferas do composto contido no dito implante. The present invention pertains to the field of subdermal hormonal implants, more particularly the invention relates to a silicone reservoir, elastomer and silver nanoparticles on a 10 nm / ml scale of Polydimethylsiloxane (PDMS). Said reservoir is in the form of a tube and has silicone with micropores which provide release of microspheres of the compound contained in said implant.
Histórico da Invenção History of the Invention
[002] A presente invenção tem com o objetivo proporcionar um implante subdérmico de liberação controlada de medicamentos para o tratamento de irregularidades menstruais, sintomas de tensão pré-menstrual e dores pélvica, entre outros sintomas relacionados à endometriose. The present invention has for the purpose of providing a controlled release drug subdermal implant for the treatment of menstrual irregularities, premenstrual tension symptoms and pelvic pain, among other symptoms related to endometriosis.
[003] É comum o uso, de forma contínua, de contraceptivos orais combinados, compostos pelos hormônios estrogênio e progesterona, com a finalidade de cessar a menstruação e, dessa forma, evitar os sintomas mencionados. Um método alternativo também já utilizado consiste na inserção de um dispositivo intrauterino (DIU) hormonal, normalmente contendo o hormônio levonogestrel. The continuous use of combined oral contraceptives, composed of the hormones estrogen and progesterone, is used in order to stop menstruation and, therefore, avoid the mentioned symptoms. An alternative method also used is the insertion of a hormonal intrauterine device (IUD), usually containing the hormone levonogestrel.
[004] Este endoceptivo é colocado dentro do útero e, através de um pequeno reservatório, libera de maneira lenta e progressiva o sal de levonogestrel, devendo ser subtituído após o período de cinco anos. Apesar de eficaz para evitar os sintomas de endometriose e como método contraceptivo, diversas pacientes relatam efeitos adversos, como sensibilidade mamária, irregularidade menstrual, sangramentos de escape e em alguns casos, o aparecimento de cistos produtores de estrogênio, que necessitam ser retirados cirurgicamente. [004] This endoceptive is placed inside the uterus and, through a small reservoir, liberates slowly and progressively the levonogestrel salt, and should be replaced after the five year period. Although effective in preventing the symptoms of endometriosis and as a contraceptive method, patients report adverse effects such as breast tenderness, menstrual irregularity, bleeding-off and, in some cases, the onset of estrogen-producing cysts that need to be surgically removed.
[005] Buscando evitar esses efeitos adversos, médicos desenvolveram outro tratamento hormonal, utilizado principalmente para prevenção de cistos. Um dos fatores considerados na elaboração do tratamento foi evitar a utilização do hormônio estrogênio e similares, já que esse está associado a maiores riscos tromboembólicos, como acidente vascular cerebral (AVC) ou trombose. Esse tratamento consiste em um implante do hormônio gestrinona e apresenta bons resultados para interrupção da menstruação e a consequente melhora de sintomas da endometriose, funcionando também como método contraceptivo. [005] Seeking to avoid such adverse effects, physicians have developed another hormonal treatment, primarily used for cystic prevention. One of the factors considered in the elaboration of the treatment was to avoid the use of the hormone estrogen and the like, since this is associated with higher thromboembolic risks, such as cerebrovascular accident (stroke) or thrombosis. This treatment consists of an implant of the hormone and has good results for the interruption of menstruation and the consequent improvement of symptoms of endometriosis, also functioning as a contraceptive method.
[006] Entretanto, ainda é um método restrito a maior parte da população. Além disso, também foram relatados efeitos adversos derivados do implante de gestrinona, principalmente efeitos androgênicos, como maior crescimento de pelos, engrossamento da voz, retenção de líquidos e aumento de peso. Ademais, há impossibilidade de retirada do implante após colocação, tendo em vista as dimensões micrométricas e por ser composto por material bioabsorvível. Caso a paciente não se adapte ao método, deve esperar o tempo natural de degradação do implante (de no mínimo quatro meses) para cessação dos efeitos. [006] However, it is still a method restricted to most of the population. In addition, adverse effects derived from the implantation of gestrinone, mainly androgenic effects, such as increased hair growth, voice thickening, fluid retention and weight gain were also reported. In addition, it is impossible to remove the implant after placement, considering the micrometric dimensions and because it is composed of bioabsorbable material. If the patient does not adapt to the method, the natural time of degradation of the implant (at least four months) should be expected to cease the effects.
[007] Considerando os efeitos adversos e impossibilidade de remoção do implante, iniciou-se o desenvolvimento do implante da presente invenção, utilizando polímeros de silicone como material, a fim de que não fosse bioabsorvível e pudesse ser retirado em qualquer momento, de acordo com o desejo da paciente e recomendação médica. Partindo de um polímero de silicone, sendo este preferencialmente o polidimetilsiloxano, foram adicionados outros componentes para promover vantagens ao reservatório. Foi formada uma blenda entre o polímero de silicone e um polímero elastômero a fim de promove uma maior flexibilidade ao implante, permitindo a liberação prolongada dos hormônios nele contidos. Considering the adverse effects and impossibility of removal of the implant, the implant of the present invention was developed by using silicone polymers as the material so that it would not be bioabsorbable and could be removed at any time, in accordance with the patient's desire and medical recommendation. Starting from a silicone polymer, this being preferably the polydimethylsiloxane, were added other components to promote reservoir advantages. A blend was formed between the silicone polymer and an elastomeric polymer in order to promote greater flexibility to the implant, allowing prolonged release of the hormones contained therein.
[008] Além disso, os polímeros utilizados são resistentes a variação de temperatura como consequência de suas características químicas, não tendo seu funcionamento comprometido pela variação da temperatura corporal. Por fim, foram acrescentadas nanopartículas de prata à cadeia de silicone, com a finalidade de promover uma ação anti-inflamatória e antimicrobiana, sendo testadas diversas concentrações até se encontrar uma concetração ideal que não afeta as propriedades da blenda polimérica e do material final. In addition, the polymers used are resistant to temperature variation as a consequence of their chemical characteristics, and their functioning is not compromised by the variation in body temperature. Finally, silver nanoparticles were added to the silicone chain in order to promote an anti-inflammatory and antimicrobial action, and several concentrations were tested until an ideal concentration that did not affect the properties of the polymer blend and the final material was found.
Estado da Técnica State of the art
[009] O documento de patente US3279996 descreve um implante terapêutico confeccionado de polisiloxano, desenhado para liberação controlada de medicamentos para ser implantado em órgão-alvo. Esse implante foi concebido para uso animal, sem maiores preocupações com a adaptação de pacientes.  US3279996 discloses a thermoformed polysiloxane therapeutic implant designed for controlled release of medicaments for implantation into a target organ. This implant was designed for animal use, without major concerns with patient adaptation.
[010] Já o implante subdérmico de liberação controlada da invenção aqui ensinada tem como objetivo a utilização em seres humanos, além de proporcionar uma melhor adaptação dos pacientes ao tratamento, com vantagens aos outros métodos já utilizados. Para isso, é utilizada uma blenda entre o polímero de silicone e um polímero elastômero, promovendo uma maior flexibilidade ao implante, além da inserção de nanopartículas de prata, a fim de garantir um efeito antimicrobiano. The controlled release subdermal implant of the invention taught herein is intended for use in humans, in addition to providing a better adaptation of the patients to the treatment, with advantages to the other methods already used. For this, a blend is used between the silicone polymer and an elastomer polymer, promoting greater flexibility to the implant, besides the insertion of silver nanoparticles, in order to guarantee an antimicrobial effect.
[011] O documento de patente US5756115 revela um implante subdérmico retangular com um núcleo central composto de uma base polimérica sintética, como polidimetilsiloxano, laterais intermediárias preparadas a partir de materiais poliméricos naturais ou sintéticos, como a celulose e uma camada externa preparada a partir de polímeros naturais ou sintéticos que permitam a difusão do medicamento. Patent US5756115 discloses a rectangular subdermal implant with a central core composed of a synthetic polymer base, such as polydimethylsiloxane, intermediate sides prepared from natural or synthetic polymeric materials such as cellulose and an outer layer prepared from natural or synthetic polymers allowing the diffusion of the medicament.
[012] Já o implante subdérmico de liberação controlada da presente invenção se difere desse implante do estado da técnica por ser composto de uma blenda entre o polímero de silicone e um polímero elastomero promovendo uma maior flexibilidade ao implante. O acréscimo de nanopartículas de prata também garante um efeito antimicrobiano. The controlled release subdermal implant of the present invention differs from this prior art implant because it is composed of a blend between the silicone polymer and an elastomeric polymer promoting greater flexibility to the implant. The addition of silver nanoparticles also ensures an antimicrobial effect.
[013] O documento de patente KR100445248A1 descreve um composto a base de polisiloxano, contendo pelo menos um metal monovalente ou bivalente como grupamento na molécula de siloxano, podendo ser esse metal cobre, prata, zinco, magnésio, cálcio ou sódio. O objetivo da adição do metal é conferir propriedades antimicrobianas ao material. Entretanto, o implante subdérmico de liberação controlada aqui ensinado é composto por uma blenda entre o polímero de silicone e um polímero elastomero, promovendo uma maior flexibilidade ao implante. Há também o acréscimo de nanopartículas de prata complexadas com o polímero, mas não ligadas quimicamente ao monômero, para garantir uma ação bactericida sem interferir nas características físicas do implante, utilizando a concentração de 10 nanômetros de prata por cada mililitro de polímero de silicone, diminuindo em no máximo 10% o escoamento do medicamento pelos microporos (se comparado ao implante sem prata). Patent document KR100445248A1 describes a polysiloxane-based compound containing at least one monovalent or bivalent metal as a grouping on the siloxane molecule, which may be copper, silver, zinc, magnesium, calcium or sodium metal. The purpose of metal addition is to impart antimicrobial properties to the material. However, the controlled release subdermal implant taught herein is composed of a blend between the silicone polymer and an elastomeric polymer, promoting greater flexibility to the implant. There is also the addition of silver nanoparticles complexed with the polymer, but not chemically bound to the monomer, to ensure a bactericidal action without interfering with the physical characteristics of the implant, using the concentration of 10 nanometers of silver per milliliter of silicone polymer, decreasing in 10% the flow of the drug by the micropores (if compared to the implant without silver).
Sumário da Invenção Summary of the Invention
[014] A presente invenção ensina um implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática constituído por uma blenda polimérica compreendendo um polímero de silicone e um elastômero, com adição de íons de prata na escala de 5 a 15 nm/ml incorporados à cadeia polimérica do silicone, sendo a adição de íons de prata preferencialmente na escala de 10 nm/ml. The present invention teaches an implant with reservoir containing micropores of prolonged release for subdermic application with thermoelastic and thermostatic properties constituted by a blend polymer composition comprising a silicone polymer and an elastomer, with addition of silver ions in the range of 5 to 15 nm / ml incorporated into the silicone polymer chain, the addition of silver ions being preferably in the range of 10 nm / ml.
[015] O polímero de silicone do presente implante em forma de tubo é preferencialmente polidimetilsiloxano. [015] The silicone polymer of the present tube-shaped implant is preferably polydimethylsiloxane.
[016] O implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica possuir formato cilíndrico com altura de 30 a 50 mm de altura e de 1 a 3 mm de diâmetro, sendo a altura preferencial do cilindro de 40 a 45 mm de altura e 2 mm de diâmetro. The implant with reservoir containing micropores of prolonged release for subdermal application has cylindrical format with height of 30 to 50 mm of height and of 1 to 3 mm of diameter, being the preferred height of the cylinder of 40 to 45 mm of height and 2 mm in diameter.
[017] A superfície externa do implante é ainda revestida com silanol (SiOH). [017] The outer surface of the implant is further coated with silanol (SiOH).
[018] A invenção ainda ensina um uso do implante no tratamento hormonal, preferencialmente para tratar a endometriose. The invention further teaches a use of the implant in the hormonal treatment, preferably to treat endometriosis.
Breve descrição das Figuras Brief description of the figures
[019] A figura 1 mostra o implante com reservatório com microporos para liberação prolongada, sendo este um tubete de silicone de forma cilíndrica, com dimensões preferenciais de 30 a 50 mm de altura e de 1 a 3 mm de diâmetro.  Figure 1 shows the implant with a micropore reservoir for extended release, this being a cylindrical silicone tube of preferred dimensions of 30 to 50 mm in height and 1 to 3 mm in diameter.
Descrição detalhada da Invenção Detailed Description of the Invention
[020] O implante em forma de tubo de silicone aqui ensinado possui propriedades termoelásticas e termostáticatermostática ou termofixa. A fim de se alcançar os efeitos aqui descritos, utiliza-se um polímero orgânico polidimetilsiloxano, polida linear de dimethylsiloxane, inerte, atóxico e não inflamável. [021] O presente tubo não altera sua forma com altas e baixas temperaturas, em vista de suas propriedades viscoelásticas à alta temperatura. A superfície externa é revestida com silanol (SiOH) a fim de que, por um determinado tempo, haja um efeito hidrofílico. Os implantes em forma de tubos possuem dureza intermediária, com capacidade de elasticidade. A elasticidade proporciona aumento de seu diâmetro para que possa comportar de 140 a 160 mg de sal medicamentoso. [020] The silicone tube-shaped implant taught here has thermoelastic and thermostatic and thermostatic properties or thermosetting. In order to achieve the effects described herein, a linear polydimethylsiloxane, polydimethylsiloxane, inert, nontoxic and nonflammable polydimethylsiloxane organic polymer is used. [021] The present tube does not change its shape with high and low temperatures, due to its viscoelastic properties at high temperature. The outer surface is coated with silanol (SiOH) so that, for a given time, there is a hydrophilic effect. Implants in the form of tubes have intermediate hardness, with elasticity. The elasticity provides an increase in its diameter so that it can contain 140 to 160 mg of medicated salt.
[022] Os tubos de silicone possuem prata na escala nanométrica, que influencia em aproximadamente em somente 10% da biodinâmica funcional do tubo. O tubete é incolor, podendo possuir tom ligeiramente amarelado em função da inserção da prata. [022] Silicon tubes have nanoscale silver, which influences in approximately 10% of the functional biodynamics of the tube. The tube is colorless and may have a slightly yellowish hue depending on the insertion of the silver.
[023] O implante de silicone com elastômero possui microporos para proporcionar a liberação de microesferas do sal a ser usado no interior do tubo. A liberação, por meio de microporos do silicone, é feita de maneira gradativa e prolongada. [023] The silicone elastomer implant has micropores to provide the release of microspheres of the salt to be used inside the tube. The release, through micropores of the silicone, is done in a gradual and prolonged manner.
[024] O reservatório em forma de um tubo cilíndrico precisa ter propriedade elásticas, sendo capaz de proporcionar passagem do sal micronizado pelos microporos do silicone. A liberação ocorrerá em um período entre 6 a 12 meses. Ou seja, a presente invenção proporciona um implante subdérmico que libera a medicação de forma constante e prolongada, com ação bactericida. The reservoir in the form of a cylindrical tube needs to have elastic properties, being able to provide passage of the micronized salt through the micropores of the silicone. The release will occur in a period between 6 to 12 months. That is, the present invention provides a subdermal implant which releases the medication in a constant and prolonged manner, with bactericidal action.
[025] A invenção trata de um tubo cilíndrico silástico, para receber uma combinação de hormônios de aplicação usualmente subcutânea. The invention is a silastic cylindrical tube for receiving a combination of usually subcutaneous application hormones.
[026] A principal finalidade do implante aqui ensinado é o tratamento mais seguro e eficiente da Endometriose, além do tratamento de outras patologias associadas. [027] O presente implante em forma de tubo de silicone é apropriado para esterilização por raios gama em altas temperaturas, sendo este considerado o melhor método de esterilização praticado na área de dispositivos médicos. [026] The main purpose of the implant here taught is the more safe and efficient treatment of Endometriosis, in addition to the treatment of other associated pathologies. The present silicone tube-shaped implant is suitable for high-temperature sterilization by gamma rays and is considered to be the best method of sterilization practiced in the area of medical devices.
[028] Dessa forma, o implante da presente invenção tem particularidade, como a colocação da prata na escala nanométrica no siloxano, não comprometendo mais que 10% da biomecânica do implante. [028] Thus, the implant of the present invention has particularity, such as the placement of silver on the nanometer scale in the siloxane, with no compromising more than 10% of the biomechanics of the implant.
[029] A prata nesta escala tem proporciona o efeito de inibir fatores pró- inflamatórios locais, também tem efeitobactericida. Sendo assim, a presente invenção proporciona menor risco de encapsulamento e rejeição do implante. Esse reservatório de preferencialmente 4,5cm terá propriedade termoelástica e não sofrerá alteração em sua funcionalidade com a colocação de até 140 - 160 mg de sais em seu interior. Os implantes serão removidos após 12 meses. Silver on this scale has the effect of inhibiting local pro-inflammatory factors, it also has bactericidal effect. Thus, the present invention provides less risk of encapsulation and implant rejection. This reservoir of preferably 4.5cm will have thermoelastic property and will not suffer alteration in its functionality with the placement of up to 140 - 160mg of salts in its interior. The implants will be removed after 12 months.
[030] Para cada paciente até 70kg será usado uma unidade. Neste implante são inseridos os sais padronizados e estudados individualmente. [030] One unit will be used for each patient up to 70kg. In this implant are inserted the standardized and individually studied salts.
[031] A presente invenção ensina então um implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática constituído por uma blenda polimérica compreendendo um polímero de silicone e um elastômero, com adição de íons de prata na escala de 5 a 15nm/ml incorporados à cadeia polimérica do silicone, sendo a adição de íons de prata preferencialmente na escala de 10nm/ml, onde o polímero de silicone do presente implante em forma de tubo é preferencialmente polidimetilsiloxano. The present invention thus teaches a reservoir implant containing long-release micropores for subdermal application with thermoelastic and thermostatic properties consisting of a polymer blend comprising a silicone polymer and an elastomer with addition of silver ions on the scale of 5 to 15nm / ml incorporated into the silicone polymer chain, the addition of silver ions being preferably in the range of 10nm / ml, wherein the silicone polymer of the present tube-shaped implant is preferably polydimethylsiloxane.
[032] O presente implante pode ser utilizado para várias medicações, não hormonais, para a liberação prolongada de medicação em pacientes que tenham a necessidade de receber medicação por via oral de forma contínua. Logo, os tratamentos de longo prazo, poderão ser feitos de maneira mais prática, além de ter o seu custo também otimizado. [032] The present implant can be used for various non-hormonal medications for the prolonged release of medication in patients who need to receive oral medication on an ongoing basis. Therefore, the long-term treatments can be done in a more practical way, in addition to having its cost optimized.

Claims

REIVINDICAÇÕES
Um implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática caracterizado por ser constituído por uma blenda polimérica compreendendo um polímero de silicone e um elastômero, com adição de íons de prata na escala de 5 a 15nm/ml incorporados à cadeia polimérica do silicone. An implant with reservoir containing long-release micropores for subdermal application with thermoelastic and thermostatic properties characterized by a polymer blend comprising a silicone polymer and an elastomer, with the addition of silver ions in the range of 5 to 15 nm / ml incorporated into the silicone polymer chain.
O implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática, de acordo com a reivindicação 1, caracterizado pelo do polímero de silicone ser polidimetilsiloxano.  The implant with reservoir containing micropores of prolonged release for subdermal application with thermoelastic and thermostatic properties, according to claim 1, characterized in that the silicone polymer is polydimethylsiloxane.
O implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática, de acordo com a reivindicação 1, caracterizado pelo fato da adição de íons de prata ser preferencialmente na escala de 10nm/ml. O implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática, de acordo com a reivindicação 1, caracterizado pelo fato do reservatório possuir formato cilíndrico com altura de 30 a 50 mm de altura e de 1 a 3 mm de diâmetro.  The implant with reservoir containing micropores of prolonged release for subdermal application with thermoelastic and thermostatic properties, according to claim 1, characterized in that the addition of silver ions is preferably in the 10nm / ml scale. The implant with reservoir containing micropores of prolonged release for subdermal application with thermoelastic and thermostatic properties, according to claim 1, characterized in that the reservoir has a cylindrical shape with a height of 30 to 50 mm in height and of 1 to 3 mm in diameter .
O implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática, de acordo com a reivindicação 4, caracterizado pelo fato da altura preferencial do cilindro ser de 40 a 45 mm de altura preferencial de 2 mm de diâmetro. O implante com reservatório contendo microporos de liberação prolongada para aplicação subdérmica com propriedades termoelásticas e termostática, de acordo com a reivindicação 1, caracterizado pelo fato da superfície externa do implante ser revestida com silanol (SiOH). The implant with reservoir containing micropores of prolonged release for subdermal application with thermoelastic and thermostatic properties, according to claim 4, characterized in that the preferred height of the cylinder is from 40 to 45 mm of preferential height of 2 mm in diameter. The implant with reservoir containing extended release micropores for subdermal application with thermoelastic and thermostatic properties, according to claim 1, characterized in that the outer surface of the implant is coated with silanol (SiOH).
Um uso do implante da reivindicação 1, caracterizado pelo fato de ser utilizado no tratamento hormonal. A use of the implant of claim 1, characterized in that it is used in hormonal treatment.
O uso do implante, de acordo com a reivindicação 7, caracterizado pelo fato de tratar a endometriose.  The use of the implant according to claim 7, wherein the endometriosis is treated.
PCT/BR2018/050161 2017-10-26 2018-05-18 Implant with reservoir containing sustained release micropores for subdermal application with thermoelastic and thermostatic properties and use of said implant WO2019079869A1 (en)

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