CN109288832A - A kind of medication coat composition and its preparation method and application for ureter bracket - Google Patents

A kind of medication coat composition and its preparation method and application for ureter bracket Download PDF

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Publication number
CN109288832A
CN109288832A CN201811286764.6A CN201811286764A CN109288832A CN 109288832 A CN109288832 A CN 109288832A CN 201811286764 A CN201811286764 A CN 201811286764A CN 109288832 A CN109288832 A CN 109288832A
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Prior art keywords
medication coat
coat composition
ureter
parts
rack body
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CN201811286764.6A
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CN109288832B (en
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夏佩佩
魏征
谢建
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Puyi (Shanghai) Biotechnology Co.,Ltd.
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Pu Yi (shanghai) Biotechnology Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/11—Pteridophyta or Filicophyta (ferns)
    • A61K36/12—Filicopsida or Pteridopsida
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/68—Plantaginaceae (Plantain Family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/898—Orchidaceae (Orchid family)
    • A61K36/8984—Dendrobium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389—The prosthesis being coated or covered with a particular material
    • A61F2310/0097—Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics

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  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Heart & Thoracic Surgery (AREA)
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Abstract

The medication coat composition and its preparation method and application that the present invention provides a kind of for ureter bracket；The medication coat composition includes following component by weight: 0.3~1.3 part of rapamycin, 0.02~0.09 part of Puerarin, 0.01~0.05 part of Formoterol, 0.2~1.5 part of anti-infectives, 2~6 parts of natural products, 1~2 part of hydrophilic polymer, 1.3~4.5 parts of additive, 20~90 parts of solvent；Medication coat composition provided by the present invention, by rapamycin, three kinds of ingredients of Puerarin and anti-infectives it is reasonably combined, not only has the function of good expansion ureter, but also have the effect of antibacterial anti-inflammatory, treatment injury of ureter, more lasting curative effect is reached so that composition has the effect of long-acting slow-release by the adjusting of hydrophilic polymer and additive simultaneously, also new strategy is provided for research and development new drug, had a good application prospect.

Description

A kind of medication coat composition and its preparation method and application for ureter bracket
Technical field
The invention belongs to medical instruments fields, are related to a kind of for the medication coat composition of ureter bracket and its preparation Method and purposes.
Background technique
Medication coat on bracket is to be coated on rack surface after directly or with polymer substrate mixing drug, makes bracket As a local drug delivery system, local concentration and the action time of therapeutic agent on the one hand can be increased in this way, it is another Aspect again can be to avoid systemic administration bring toxic side effect.
It is counted according to clinical data, the postoperative ureterostenosis of ureteral calculi is common long term complication, either open Stone is taken still to take stone, endoscopic lithotripsy through hysteroscope, ureterostenosis incidence is 10% or so.With opening for intracavitary Urology Surgery The disease incidence of exhibition, the injury of ureter caused by performing the operation significantly rises.Injury of ureter caused by surgical procedure, generally not in art It is easily found, occurs that symptom is narrow to be just checked through until postoperative.
Most of ureterostenosis are posteriority and usually iatrogenic.The most common cause of disease of ureterostenosis It is damaged during being endoscope (open) or laparoscopically surgical operation.
Ureter bracket is most common tool in various benign and malignant disease in the urological system treatments.However bracket makes With being often accompanied with some complication, such as leather shell formation, infection, pain, urine are backflowed, stent migration or failure.These Complication largely will affect the disease therapeuticing effect and quality of life of patient.The rami ureterici of domestic and international application at present Frame is acted on without drug therapy, for injury of ureter, it is narrow cannot play the role of it is effective, and as ureter bracket is implanted into The extension of time, surrounding catheter often will form tissue cladding, bacterial biof iotalm etc. and cause to infect, and cause other complication.
And it is coated with medication coat in rack surface, it is positive for overcoming defect existing for current bracket to have the function of.
CN105031741A discloses a kind of coating containing anti-infectives, has the medical catheter and its system of slow releasing pharmaceutical function Preparation Method.The coating containing anti-infectives has the medical catheter of slow releasing pharmaceutical function, is to coat one on medical catheter surface Obtained by micro-capsule coating of the layer containing anti-infectives.But this method is to immerse administration, it is uneven to will lead to medication coat, makes It can not equal control at release.
In addition, at present studies have reported that the correlation of preparation and the drug release behavior of adriamycin coating ureter bracket is ground Study carefully, which employs solution dipping methods to be prepared for adriamycin coating ureter bracket, and is gone out by ethylene oxide sterilizing mode Bacterium.Adriamycin coating bracket drug release behavior in artificial urine is had studied, has been inquired at drugloading rate and ethylene oxide sterilizing Manage the influence to adriamycin drug release behavior.The result shows that the increase of drugloading rate can reduce the rate of release of drug, and epoxy Ethane sterilizing can be such that adriamycin rate of release accelerates.The method equally exist drug release can not equal control defect, and Curative effect is poor.
Therefore, a kind of novel medication coat how is developed, for being applied in ureter bracket, treats ureterostenosis Have great importance with damage.
Summary of the invention
For the deficiency of prior art, the purpose of the present invention is to provide a kind of medication coat groups for ureter bracket Close object and its preparation method and application.
To achieve this purpose, the present invention adopts the following technical scheme:
In a first aspect, the medication coat composition is by weight the present invention provides a kind of medication coat composition Including following component:
Medication coat composition provided by the invention passes through rapamycin, Puerarin and anti-infectives three kinds of ingredients It is reasonably combined, not only have the function of good expansion ureter, but also the effect with antibacterial anti-inflammatory, treatment injury of ureter Fruit, while passing through the adjusting of hydrophilic polymer and additive, so that composition has the effect of long-acting slow-release, reach more persistently Curative effect.
The parts by weight of rapamycin be 0.3~1.3 part, such as can be 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1.0 parts, 1.1 parts, 1.2 parts or 1.3 parts etc..
The parts by weight of Puerarin be 0.02~0.09 part, such as can be 0.02 part, 0.03 part, 0.04 part, 0.05 part, 0.06 part, 0.07 part, 0.08 part or 0.09 part etc..
Puerarin is the isoflavonoid derivatives with coronary dilatation effect separated from Chinese medicament kudzu-vine root.With bring down a fever, it is calm With make the increased effect of coronary blood flow, have protective effect to Acute myocardial bleeding caused by pituitrin.Clinically For coronary disease and angina pectoris, hypertension.Currently, proving that Puerarin can be gentle to rabbit arterial smooth muscle in vitro test in vivo Road smooth muscle generates emulative beta-receptor antagonism.
Puerarin itself has angiectatic effect, but there is presently no any research shows that Puerarin can achieve Expand the effect of ureter.
And it is an unexpected discovery of the invention that Puerarin can promote promoted rapamycin treatment and expand ureter effect, Compared to rapamycin is used alone, effect is more prominent, and will not generate excessive toxic side effect.
The parts by weight of Formoterol are 0.01~0.05 part, such as can be 0.01 part, 0.02 part, 0.03 part, 0.04 part Or 0.05 part etc..
Formoterol has strongly and lasting bronchiectatic activity, is a kind of long-acting β2Receptor stimulating agent, molecule There is longer side chain in structure, therefore have stronger fat-soluble and to β2Receptor higher selectivity.Such drug can be with β on air flue target cell membrane2Receptor combines, activation excitability G-protein, adenosine cyclase of acid, ATP conversion in activated cell For cAMP, intracellular cAMP level increases, and then activates cAMP dependent kinases (PKA), dense by intracellular free calcium The decline of degree, the approach such as myosin light chain kinase (MCLK) inactivation and potassium channels opening, final relaxing smooth muscle.But it is such Drug does not have anti-inflammatory effect.
A small amount of Formoterol is added in the present invention, and the bronchiectatic activity having using Formoterol itself can Promote the mixture of rapamycin and Puerarin, further promotes the effect of expansion ureter.
The parts by weight of anti-infectives are 0.2~1.5 part, such as can be 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 Part, 0.7 part, 0.8 part, 0.9 part, 1.0 parts, 1.1 parts, 1.2 parts, 1.3 parts, 1.4 parts or 1.5 parts etc..
In the present invention, due to drug relevant to expansion ureter, hardly there is anti-inflammatory, antibacterial effect, therefore in group It closes in object and is added to suitable anti-infectives, to have the function that antibacterial anti-inflammatory.
Preferably, the anti-infectives include glucocorticoid, sulphadiazine, rifampin, chlorhexidine, triclosan or salt Any one in sour minocycline.
Wherein, glucocorticoid can be dexamethasone, momestasone furoate, prednisone, meprednisone, betamethasone or hydrogen Change cortisone etc..Generally preferably use dexamethasone or momestasone furoate.
The parts by weight of natural products be 2~6 parts, such as can be 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts or 6 parts etc..
Preferably, the natural products includes chingma abutilon seed, lophatherum gracile, rhizoma imperatae, semen plantaginis, endothelium corneum gigeriae galli, Lygodium japonicum or stone In dry measure used in former times any one or at least two combination.
Preferably, the natural products is chingma abutilon seed, lophatherum gracile, rhizoma imperatae and the combination of semen plantaginis.
In the present invention, it is preferred to above-mentioned four kinds of natural products collaboration has reducing fever and causing diuresis, invigorates the spleen and benefits qi, the function that excreting dampness is treating stranguria Effect, can play good reparation damaging action in ureter.
The parts by weight of hydrophilic polymer are 1~2 part, such as can be 1 part, 1.1 parts, 1.2 parts, 1.3 parts, 1.4 parts, 1.5 Part, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts or 2 parts etc..
Preferably, the hydrophilic polymer includes polyvinylpyrrolidone and/or polyoxyethylene hydrophilic polymer.
Polyoxyethylene hydrophilic polymer can be polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitol acid anhydride Monopalmitate, polyoxyethylene sorbitan monostearate etc..
The parts by weight of additive are 1.3~4.5 parts, such as can be 1.3 parts, 1.5 parts, 1.8 parts, 2 parts, 2.3 parts, 2.5 Part, 2.8 parts, 3 parts, 3.4 parts, 3.5 parts, 3.8 parts, 4 parts, 4.2 parts, 4.3 parts, 4.4 parts or 4.5 parts etc..
Preferably, the additive includes any one in D-sorbite, anhydrous sorbitol or xylitol or at least two The combination of kind.
D-sorbite has good performance of keeping humidity, and food can be made to keep certain moisture, prevents drying, can also prevent sugar, The precipitations such as salt crystallization.Anhydrous sorbitol is existed in the form of sorbitan fatty acid ester.Xylitol has hygroscopicity, is dissolved in Amount of heat is can absorb when water.
Above-mentioned small molecule can promptly be spread.They easily can discharge itself from delivering sacculus, to make drug Release accelerate, and they can diffuse out drug in the tissue of drug conjugates chamber, improve or promote drug mobile Tissue is penetrated across the polar head group of water barrier and double-layer of lipoid.Hydroxyl is as hydrophilic segment, because it can not It is reacted with water soluble drug such as rapamycin.D-sorbite and xylitol have in spatial configuration all in the same side of molecule On three neighbouring hydroxyls, by the improved compatibility for bringing water soluble drug and hydrophilic additive and improved drug Tissue intake and absorb.
Preferably, the mass ratio of the additive and hydrophilic polymer be (0.05~3): 1, for example, can be 0.05:1, 0.06:1、0.08:1、0.1:1、0.3:1、0.4:1、0.8:1、0.9:1、1:1、1.5:1、1.6:1、1.9:1、2.3:1、2.5: 1,2.8:1 or 3:1 etc..
In the present invention, additive and hydrophilic polymer can form inflated condition in reaching ureter behind target position, It ensure that the expansion state of ureter, and rapamycin, anti-infectives and natural products smoothly can be discharged and be absorbed, have There is positive therapeutic effect.
Preferably, the solvent includes water, methanol, ethyl alcohol, normal propyl alcohol, isopropanol, acetone, methylene chloride, dimethyl Asia In sulfone or acetonitrile any one or at least two combination.
Second aspect, the present invention provides a kind of preparation methods of medication coat composition as described in relation to the first aspect, will Rapamycin, Puerarin, Formoterol, anti-infectives, natural products are dissolved in solvent according to the ratio, then by the parent of proportional quantity Aqueous polymer, additive are added in solvent, and mixing forms uniform mixed solution and obtains the medication coat composition.
Preferably, the mixed temperature is 40~60 DEG C, such as can be 40 DEG C, 43 DEG C, 45 DEG C, 48 DEG C, 49 DEG C, 50 DEG C, 53 DEG C, 54 DEG C, 55 DEG C, 56 DEG C, 57 DEG C, 58 DEG C, 59 DEG C or 60 DEG C etc..
Preparation method provided by the invention, it is simple and easy.But in mixing, should keep within the said temperature range, it is no Then hydrophilic polymer, additive and the aqueous solution containing drug are unable to reach optimal solute effect, will cause shape when in use At coating unevenness consequence, influence play curative effect.
The third aspect, the present invention provides a kind of ureter bracket, the ureter bracket includes rack body, bracket sheet The medication coat and slow release layer that the medication coat composition as described in first aspect that body surface face is set gradually from inside to outside is formed.
Preferably, the rack body is linear hollow tubular structure, and the both ends of the rack body have positioning function Structure, the medication coat composition are attached on the outer surface of rack body.
In the present invention, location structure is generally cricoid structure, is set to the both ends of rack body.
Preferably, the rack body is single layer structure or multilayered structure.
In the present invention, rack body is that single layer refers to the rack body that monolayer material is prepared；And multilayered structure Rack body be then, using identical material, to overlap to form multilayered structure in preparation process.
Preferably, the rack body is provided with anti-recirculation device in tail end.
Preferably, it includes several protrusions and the layer for having at least one aperture that the slow release layer, which is surface,.
Preferably, the raw material for preparing of the slow release layer is any one in polylactic acid, copolymer of poly lactic acid or chitosan. Use polylactic acid or chitosan to prepare raw material as slow release layer, can reach biodegradable effect.
Wherein, it is total to can be poly lactide-glycolide acid, polyethylene glycol monomethyl ether-polylactic acid for copolymer of poly lactic acid Polymers or polyethylene glycol-polylactic acid copolymer etc..
In the present invention, the meaning that several protrusions are contained on surface is to be bonded on medication coat surface by polylactic acid shape At slow release layer, the layer of a formation not instead of smooth layer, the state that height rises and falls can shape also, in each protrusion At at least one aperture, when fluid passes through protrusion, biggish active force can be generated, into aperture, such medication coat can lead to Small holes are contacted with the formation of the fluid of target site, achieve the purpose that sustained-release administration.And the existing coating stent of medicine of mesh, it is Medication coat is directly directly acted on into region of interest, drug effect is shorter, is unfavorable for sustained-release and controlled release.
In the present invention, the size of slow release layer protrusions can be uniform or inhomogenous.Generally protrusion is big It is small between 0.02~2mm.
In the present invention, ureter bracket is optionally provided with the devices such as boost tube, convenient for it is actual operation and it is subsequent It uses.
There are many ways to being attached to medication coat composition on ureter bracket, such as spraying, dip-coating, Electrostatic Absorption Etc..It selects which kind of attachment techniques to depend primarily on the viscosity and surface tension of composition, and is generally preferred to spray or soak It applies.And the coating uniform that final composition should be made to be formed on ureter bracket.The thickness of the coat of formation is usually 0.1~20 μm is differed.
Fourth aspect, the present invention provides a kind of medication coat compositions as described in relation to the first aspect to treat urine output in preparation Manage the purposes in narrow and damage drug.
Currently, the effect that treatment ureterostenosis and the drug of damage have very much, but be single use can not reach most Good effect, and act on more single.And medication coat composition provided by the invention, it not only can be used as ureter bracket Medication coat use, drug can also be developed into and used.
Medication coat composition is such as prepared into liquid preparation or is baked to be prepared into solid pharmaceutical preparation, is applied to Clinical treatment.The preparation method of related preparations can be realized by the preparation process of those skilled in the art's routine.
Compared with the existing technology, the invention has the following advantages:
Medication coat composition provided by the invention passes through rapamycin, Puerarin and anti-infectives three kinds of ingredients Reasonably combined, the reasonably combined use of glucocorticoid especially in anti-infectives not only has good expansion ureter Effect, but also have the effect of antibacterial anti-inflammatory, treatment injury of ureter, while passing through the tune of hydrophilic polymer and additive Section, so that composition has the effect of long-acting slow-release, reaches more lasting curative effect.
Medication coat composition provided by the invention can expand the drug for being prepared into a variety for the treatment of related diseases, to grind Study carefully developing new drug and provide new strategy, has a good application prospect.
Ureter bracket provided by the invention, by being provided with special slow release layer, so that medication coat can either be formed Effectively administration, and slow release effect can be reached, action time is extended, the guarantor provided for practical application and control related symptoms Barrier.
Detailed description of the invention
Fig. 1 is the ureter bracket schematic diagram that the embodiment of the present invention 5 provides, 1- rack body, 102- location structure.
Fig. 2 is the ureter bracket schematic diagram with the anti-bag that backflows that the embodiment of the present invention 5 provides, 1- rack body, The anti-recirculation device of 101-, 102- location structure.
Fig. 3 is the ureter bracket surface part stratiform figure that the embodiment of the present invention 5 provides, 1- rack body, the painting of 2- drug Layer, 3- slow release layer.
Fig. 4 is the ureter bracket surface part stratiform figure that comparative example 5 of the present invention provides, 1- rack body, the painting of 2- drug Layer.
Specific embodiment
The technical scheme of the invention is further explained by means of specific implementation.Those skilled in the art should be bright , the described embodiments are merely helpful in understanding the present invention, should not be regarded as a specific limitation of the invention.
Embodiment 1
Medication coat composition provided in this embodiment includes following components by weight
By rapamycin, Puerarin, Formoterol, dexamethasone, chingma abutilon seed, lophatherum gracile, rhizoma imperatae and (4 kinds of semen plantaginis The mass ratio of natural products is identical) it is soluble in water according to the ratio, then the polyvinylpyrrolidone of proportional quantity, D-sorbite are added Into water, mixing forms uniform mixed solution and obtains medication coat composition at 50 DEG C.
Embodiment 2
Medication coat composition provided in this embodiment includes following components by weight
By rapamycin, Puerarin, Formoterol, triclosan, chingma abutilon seed, lophatherum gracile and Lygodium japonicum (3 kinds of natural products matter Amount is than identical) it is dissolved in ethyl alcohol according to the ratio, then the polyvinylpyrrolidone of proportional quantity, xylitol are added in ethyl alcohol, Mixing forms uniform mixed solution and obtains medication coat composition at 60 DEG C.
Embodiment 3
Medication coat composition provided in this embodiment includes following components by weight
By rapamycin, Puerarin, Formoterol, rifampin, dendrobium nobile, lophatherum gracile and Lygodium japonicum (3 kinds of natural products quality Than identical) it is dissolved in isopropanol according to the ratio, then the polyoxyethylene sorbitan monostearate of proportional quantity, xylitol are added Into isopropanol, mixing forms uniform mixed solution and obtains medication coat composition at 40 DEG C.
Embodiment 4
Medication coat composition provided in this embodiment includes following components by weight
By rapamycin, Puerarin, Formoterol, momestasone furoate, chingma abutilon seed, lophatherum gracile, rhizoma imperatae and semen plantaginis (4 The mass ratio of kind natural products is identical) it is soluble in water according to the ratio, then the polyvinylpyrrolidone of proportional quantity, D-sorbite are added Enter into water, mixing forms uniform mixed solution and obtains medication coat composition at 50 DEG C.
Comparative example 1
The difference of this comparative example and embodiment 1 is only that this comparative example does not include polyvinylpyrrolidone, dexamethasone.
Comparative example 2
The difference of this comparative example and embodiment 1 is only that this comparative example does not include D-sorbite.
Comparative example 3
The difference of this comparative example and embodiment 1 is only that this comparative example does not include Puerarin.
Comparative example 4
The difference of this comparative example and embodiment 1 is only that this comparative example does not include momestasone furoate.
The medication coat composition that embodiment 1-4 is prepared with comparative example 1-4 is tested for the property.Test method are as follows: point Not by above-mentioned several drugs coating composition even application on the ureter bracket of identical standard, sterilizing carries out zoopery.
The ureter bracket for spraying 8 kinds of different pharmaceutical coating compositions is inserted into the ureter of dog, wherein 8 dogs have There is the injury of ureter of about 20%~50% area, while being tested, measures the repair rate of injury of ureter after 1 month again (injury repair rate refers to will be compared to the damaged area of original ureter, the opposite real area accounting repaired；Practical animal is real In testing, the injury of ureter area of model dog is not easy to control, generally causes injury of ureter using physical method, as long as and With a certain proportion of damaged area, drug can play therapeutic effect to observing that repairing effect can be used as model, because This model dog for being typically chosen 20%~50% area is used to test, and measurement repair rate is relatively reasonable).The result specifically obtained is such as Shown in the following table 1:
Table 1
By the comparison of embodiment 1-4 and comparative example 1-4 it is found that medication coat composition provided by the invention, is applied to When on ureter bracket, injury of ureter can be effectively treated.And if having lacked dexamethasone (sugared cortical hormone in composition Element), momestasone furoate (glucocorticoid), Puerarin, polyvinylpyrrolidone or when D-sorbite, curative effect is poor, especially When being the absence of glucocorticoid or Puerarin, repairing effect declines to a great extent.Illustrate that the present invention passes through rapamycin, pueraria lobata Element and glucocorticoid three, collaboration have played curative effect, under the effect that lacks any of them and will cause reparation, treatment Drop.The reparation and treatment of injury of ureter is greatly facilitated in medication coat composition provided by the invention.
Embodiment 5
The present embodiment provides a kind of ureter brackets
Ureter bracket ontology 1 is linear hollow tubular structure, and the bending two ends of rack body 1 circlewise, form positioning Structure 102, specifically as shown in Figure 1, the medication coat that the medication coat composition of above-mentioned preparation is formed is attached to rack body 1 On outer surface；
In addition, ureter bracket ontology 1 can also be additionally provided with anti-recirculation device 101, the position of setting is ureter Tail end.
Wherein Fig. 3 be ureter bracket surface layer partial enlarged view, by stent inner surface be successively outward rack body 1, Medication coat 2 and slow release layer 3, the part that slow release layer 3 protrudes are provided with several apertures.
Comparative example 5
This comparative example provides a kind of ureter bracket of conventional structure
Ureter bracket ontology 1 is linear hollow tubular structure, and circlewise, medication coat 2 adheres to the bending two ends of bracket In on the outer surface of rack body 1, ureter bracket overall structure that this comparative example provides with it is almost the same in embodiment 5, only One difference be do not include slow release layer 3, the partial enlarged view on specific ureter bracket surface layer is as shown in Figure 4.
The ureter bracket that embodiment 5 and comparative example 5 are provided carries out zoopery, is compared using animal kennel as model It is found that the ureter bracket of comparative example 5 does not have a slow release effect completely, and ureter bracket provided by the invention, have good Slow release effect.
The Applicant declares that the present invention is explained by the above embodiments the medication coat for ureter bracket of the invention Composition and its preparation method and application, but the invention is not limited to above-mentioned method detaileds, that is, do not mean that the present invention is necessary Relying on above-mentioned method detailed could implement.It should be clear to those skilled in the art, any improvement in the present invention, right The equivalence replacement of each raw material of product of the present invention and addition, the selection of concrete mode of auxiliary element etc., all fall within guarantor of the invention It protects within range and the open scope.

Claims (10)

1. a kind of medication coat composition, which is characterized in that the medication coat composition includes following component by weight:
2. medication coat composition according to claim 1, which is characterized in that the anti-infectives include sugared cortical hormone Any one in element, sulphadiazine, rifampin, chlorhexidine, triclosan or minocycline hydrochloride.
3. medication coat composition according to claim 1 or 2, which is characterized in that the natural products include chingma abutilon seed, In lophatherum gracile, rhizoma imperatae, semen plantaginis, endothelium corneum gigeriae galli, Lygodium japonicum or dendrobium nobile any one or at least two combination；
Preferably, the natural products is chingma abutilon seed, lophatherum gracile, rhizoma imperatae and the combination of semen plantaginis.
4. medication coat composition according to any one of claim 1-3, which is characterized in that the hydrophilic polymer packet Include polyvinylpyrrolidone and/or polyoxyethylene hydrophilic polymer.
5. medication coat composition described in any one of -4 according to claim 1, which is characterized in that the additive includes mountain In pears sugar alcohol, anhydrous sorbitol or xylitol any one or at least two combination；
Preferably, the mass ratio of the additive and hydrophilic polymer is (0.05~3): 1.
6. medication coat composition according to any one of claims 1-5, which is characterized in that the solvent include water, Any one in methanol, ethyl alcohol, normal propyl alcohol, isopropanol, acetone, methylene chloride, dimethyl sulfoxide or acetonitrile or at least two Combination.
7. the preparation method of medication coat composition according to claim 1 to 6, which is characterized in that by thunder pa Mycin, Puerarin, Formoterol, anti-infectives, natural products are dissolved in solvent according to the ratio, then by the hydrophilic poly- of proportional quantity Conjunction object, additive are added in solvent, and mixing forms uniform mixed solution and obtains the medication coat composition；
Preferably, the mixed temperature is 40~60 DEG C.
8. a kind of ureter bracket, which is characterized in that the ureter bracket includes rack body, rack body surface by introversion The medication coat and slow release layer formed by medication coat composition of any of claims 1-6 set gradually outside.
9. ureter bracket according to claim 8, which is characterized in that the rack body is linear hollow tubulose knot The both ends of structure, the rack body have positioning function structure, and the medication coat composition is attached to the appearance of rack body On face；
Preferably, the rack body is single layer structure or multilayered structure；
Preferably, the rack body is provided with anti-recirculation device in tail end；
Preferably, it includes several protrusions and the layer for having at least one aperture that the slow release layer, which is surface,；
Preferably, the raw material for preparing of the slow release layer is any one in polylactic acid, copolymer of poly lactic acid or chitosan.
10. medication coat composition according to claim 1 to 6 is in preparation treatment ureterostenosis and damage Drug in purposes.
CN201811286764.6A 2018-10-31 2018-10-31 Medicinal coating composition for ureteral stent and preparation method and application thereof Active CN109288832B (en)

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CN109621014A (en) * 2019-02-20 2019-04-16 浦易（上海）生物技术有限公司 A kind of preparation method and drainage tube of drainage tube
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WO2023103946A1 (en) * 2021-12-06 2023-06-15 易浦润（上海）生物技术有限公司 Method for preparing controlled-release coating and coating apparatus therefor

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