100 results about "Drug content" patented technology

The invention discloses an anti-idiotypic antibody and application, the provided anti-idiotypic antibody is a monoclonal antibody capable of being specifically combined with a corresponding PD-L1 antibody drug, and the content of the antibody drug in a human body is reflected through the anti-idiotypic antibody; the anti-idiotype antibody disclosed by the invention is prepared by adopting a hybridoma technology, and an ADA kit adopting the antibody can quantitatively detect the concentration level of a PD-L1 antibody drug in vivo, and has a remarkable effect in pharmacokinetic research.

The present application belongs to the technical field of pharmaceutical preparations, and specifically provides a compound SYN045 soft capsule and a preparation method thereof. The present application adopts a fixed proportion of plant oil and polyoxyethylene glyceryl oleate combination to prepare the content, which helps to reduce the degradation of SYN045 in the content drug solution, ensures the stability of the active ingredient, and obtains a compound SYN045 soft capsule with good drug dissolution, high drug content, low impurity generation, and high bioavailability. Further, through prescription optimization of the soft capsule shell, a fixed proportion of plasticizer is selected, the mass ratio of glycerol and sorbitol is 1:2-3, the transfer of the compound SYN045 to the soft capsule shell is reduced, and thus the quality stability problem of the soft capsule preparation product during drug storage is solved.

The invention discloses a pretreatment method and application of a mirabegron resin compound, and relates to the pretreatment method of the mirabegron resin compound, which comprises the following steps: extracting the mirabegron resin compound by an extraction solvent to obtain a sample to be detected for detection; wherein the extraction solvent comprises an aprotic solvent, an ionized solvent and a counter-ion solvent. According to the method, a multi-factor synergistic strategy is adopted, the extraction time of mirabegron in the mirabegron resin compound is remarkably shortened, the medicine extraction efficiency is remarkably improved, the extraction method is high in recovery rate, meanwhile, comprehensive optimization of quality is ensured, a foundation is laid for accurate determination of the medicine content, the consistency of the medicine effect is ensured, and the method is suitable for large-scale popularization and application. The requirements of links such as drug research and development, production and quality control are met.

A method for measuring drug content indexes of a non-viral nucleic acid vector composition, comprising performing labeling by enabling a permeable nucleic acid dye to be in contact with a non-viral nucleic acid vector (for example, an mRNA-LNP). The drug content indexes are calculated by measuring, at a single-particle level, fluorescent light generated by free nucleic acids of a nucleic acid vector, and fluorescent light generated by externally adsorbed nucleic acids and internally entrapped nucleic acids of the non-viral nucleic acid vector. The drug content indexes include a drug loading capacity, entrapment efficiency and the like. The method optionally further comprises: treating a sample with a nuclease before or after performing labeling by using the permeable nucleic acid dye, and when performing treatment with the nuclease, measuring the fluorescence condition of the non-viral nucleic acid vector composition; or enabling the permeable nucleic acid dye to be in contact with the sample, and then measuring the fluorescence condition of the non-viral nucleic acid vector composition.

The present invention relates to a pharmaceutical composition which does not undergo rapid initial burst release of a drug by comprising sustained release microspheres consisting of texipatide or a pharmaceutically acceptable salt thereof, an initial burst release inhibitor, and a biodegradable polymer, has a high drug content with respect to particle size, and has high bioavailability, thus, the composition can minimize patient pain and inflammatory response that may occur when administered to a human body, and thus can be effectively used in the prevention or treatment of diabetes, beta cell dysfunction, hypertension, hyperlipidemia, obesity, and non-alcoholic steatohepatitis.

The utility model relates to the technical field of anthelmintics, and discloses a feed anthelmintics blending and mixing device which comprises a mixing barrel, a feeding pipe and a discharging pipe are arranged on one side of the upper end of the mixing barrel and the middle of the lower end of the mixing barrel respectively, a barrel cover is detachably arranged at the upper end of the mixing barrel, a pesticide feeding pipe is arranged above the barrel cover, and a stirring shaft is rotatably connected to the middle of the lower portion of the barrel cover. The stirring shaft is driven by a motor fixedly arranged above the barrel cover, a spiral stirring blade is fixedly arranged on the stirring shaft, a square stirring frame is arranged on the stirring shaft and located on the outer side of the spiral stirring blade, a plurality of stirring blocks are arranged on two side plates of the square stirring frame, and a plurality of barrier strips are arranged on the inner wall of the mixing barrel. The stirring device has the advantages that the stirring effect on feed and anthelmintic is good, the uniformity is high, and the situation that the local drug content is too high is prevented.

The invention provides a tamsulosin hydrochloride sustained release preparation and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The preparation method comprises the following steps: spraying an ethanol water solution of tamsulosin hydrochloride on a mesoporous silica carrier, and drying to obtain a drug-containing carrier; mixing the drug-containing carrier, an auxiliary carrier, an adhesive and water, and carrying out wet granulation to obtain a drug-containing soft material; extruding and rounding the medicine-containing soft material to obtain a medicine-containing pellet core; coating the drug-containing pellet core with a coating solution to obtain a coated pellet core; the coating liquid comprises an enteric-coated material and a plasticizer; and mixing the coated pellet core with a lubricant to obtain the tamsulosin hydrochloride sustained release preparation. The tamsulosin hydrochloride sustained-release preparation prepared by the method is good in drug content stability, stable in main drug release, simple in process, high in controllability and suitable for industrial production.

The application provides an ambroxol oral dissolving film composition, a preparation method and application thereof. The ambroxol oral dissolving film composition comprises an active drug, a film forming material and a taste masking agent, and the active drug is 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine and / or a pharmaceutically acceptable salt thereof, for example, ambroxol hydrochloride. The ambroxol oral dissolving film composition provided by the application has the advantages of thin thickness, good taste, stable properties, immediate dissolution in the oral cavity without drinking water, and fast oral absorption speed. Moreover, the ambroxol oral dissolving film composition has the advantages of simple process, high drug loading, good drug content uniformity, and good market prospect.

The invention provides a medicine content detection method combining a respiration simulation device and HPLC (High Performance Liquid Chromatography), which relates to the technical field of medicine detection and comprises the following steps: establishing a mathematical expression of a target medicine net peak area and a target medicine concentration under each respiration parameter combination and a mapping relation between the respiration parameter combination and a target medicine reference peak area; therefore, the target drug net peak area of the to-be-detected gas is determined, a plurality of similar breathing parameter combinations similar to the breathing state under the current breathing parameter combination are screened out, and the accurate value of the target drug concentration of the to-be-detected gas is determined by combining the corresponding confidence coefficient, so that the accuracy of the detection result is ensured, and the detection efficiency is improved. A mathematical expression for solving the target drug concentration under the current breathing parameter combination is established without multiple calibration tests, so that the workload is greatly reduced, and the drug concentration detection efficiency is improved.

The application discloses a multi-module cooperative medicine content uniformity detection pretreatment system and method, and belongs to the technical field of medicine detection. The system comprises a container processing module, a fluid processing module, a constant volume module, a mixing module, a transfer module and a control system. The container processing module realizes automatic cap pulling and cap pressing of non-standard capacity bottles; the fluid processing module realizes liquid injection and pipetting; the constant volume module realizes automatic constant volume through visual identification; the mixing module realizes automatic liquid mixing; the transfer module automatically transfers containers between modules; the control system determines the operation sequence, controls the transfer module to sequentially transfer the containers and triggers each module to perform operations, and simultaneously receives state feedback. Through multi-module cooperative linkage, the application realizes full-process automation of plaster medicine detection pretreatment without manual intervention, significantly improves processing efficiency, precision and consistency, and has state monitoring and data tracing functions.

The invention relates to a suture thread material comprising at least one polymer and at least one eutectic mixture. The polymer can be a biocompatible polymer such as polycaprolactone or PLGA. The eutectic mixture comprises triclosan. Other eutectic mixtures can be used in suture thread materials to reduce SSis and / or to decrease pain and / or to increase lubricity of sutures. The invention also provides a method for the production of sutures with drug loadings, the method comprising the use of therapeutic deep eutectic solvent (THEDES) technology to significantly increase drug content in suture matrices.

The invention provides Qingkailing dropping pills and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine extraction and preparations, the Qingkailing dropping pills comprise the following raw materials: cholic acid, nacre mother of pearl, hyodeoxycholic acid, cape jasmine, cornu bubali, isatis root, baicalin and honeysuckle; the preparation method comprises the following steps: providing pill paste powder, wherein the pill paste powder is prepared by sequentially drying mixed thick paste under reduced pressure and crushing; the mixed thick paste comprises the following raw materials: a honeysuckle extract, an isatis root-cape jasmine extract, a buffalo horn-nacre mother-of-pearl extract and a cholic acid-baicalin concentrated solution; providing a matrix, and melting and mixing the matrix with the pill paste powder to prepare a molten liquid; and providing a condensing agent, dropwise adding the molten liquid into the condensing agent, and carrying out shrinkage molding, so as to obtain the finished product dropping pill, namely the Qingkailing dropping pill. According to the preparation method, the melting and mixing efficiency and effect of the pill paste powder and the matrix are improved, the texture of molten liquid is more uniform, the content distribution of all effective components is more uniform, the medicine content uniformity in the finished dropping pill is improved, and the obtained finished dropping pill is high in stability, round in appearance and good in uniformity.

The invention discloses an automatic granulation process of a boiling granulation dryer. The automatic granulation process comprises the following steps: S1, building a granulation system; s2, when a fluidized bed is preheated to the feeding temperature, powder is fed into the fluidized bed, and then the powder is heated to the set material temperature; s3, starting automatic segmented granulation; s4, the materials are dried for t5 minutes in a delayed mode; s5, starting material coloring; s6, drying the materials for t7 minutes; and S7, the air inlet temperature is reduced, dry cold air is conveyed into the fluidized bed, the material temperature is reduced, and when the material temperature is smaller than or equal to the discharging temperature value, shutdown is conducted, and the materials are output. According to the invention, the traceability and reducibility of batch products are ensured, and the defects of manual operation are overcome; in the granulating process, the material bed collapse is avoided, and the fullness and uniformity of the medicine component of each granule are ensured.

The invention provides a GK001 solid preparation as well as a preparation method and application thereof. The solid preparation comprises the following components: a GK001 amorphous solid dispersion, an excipient, a diluent, a disintegrating agent and a lubricant, the GK001 has a structure as shown in a formula I which is described in the specification. According to the invention, GK001 is creatively prepared into a solid preparation in the form of amorphous solid dispersion, and the solid preparation has excellent stability and fluidity and high oral availability. The preparation is moderate in hardness and stable in quality, the process requirements are met, and the friability and disintegration time limit both meet the requirements; the dissolution rate of the preparation is basically consistent with the drug content, the plasma exposure is high, and the oral dose of the drug and the plasma exposure are in a linear relationship.

The invention discloses a preparation method of inositol nicotinate tablets, and belongs to the technical field of pharmaceutical preparations. By optimizing the existing process and coating components, stable dissolution of drugs is realized, and the method comprises the following steps: dispersing inositol nicotinate in mixed oil to prepare an oil phase, mixing and emulsifying the oil phase and a water phase, performing spray drying to obtain drug milk powder, coating the drug milk powder with modified chitosan, and directly tabletting the coated drug milk powder and auxiliary materials. The preparation method comprises the following steps: uniformly dispersing inositol nicotinate in mixed oil to promote the inositol nicotinate to maintain the uniformity of the drug content in the subsequent process, and adsorbing solid particles on the surfaces of drug-containing oil drops through an emulsification technology to protect the drug components; coating components are reasonably designed, so that fixed-point release of the medicine is realized, the medicine is endowed with anti-pressure ability, and the medicine can be directly tableted; and the coated medicine particles are mixed with auxiliary materials and then are directly tableted, so that the process is simplified, and the coating structure of the medicine particles is protected at the same time. The preparation method can prepare the inositol nicotinate tablet with stable drug dissolution, and the inositol nicotinate tablet is good in taste and small in stimulation to gastric mucosa.

The invention relates to the technical field of progesterone sustained-release nanoparticle production, in particular to a progesterone sustained-release nanoparticle which comprises progesterone and further comprises solid lipid and liquid lipid according to the formula ratio of 1: 1.4: 1.2: 0.8. A preparation method of the progesterone sustained-release nanoparticle comprises raw material preparation of progesterone, solid lipid and liquid lipid and melt emulsification. The prepared progesterone lipid nanoparticles have high drug entrapment efficiency which can reach 77.48% at most, and have obvious drug sustained and controlled release performance, although the particle size of the nanoparticles is increased along with the increase of the content of liquid lipid-oleic acid in the lipid nanoparticles, the drug entrapment efficiency is improved, the in-vitro release of the drug is accelerated, and the progesterone lipid nanoparticles have good application prospects. According to the progesterone nanostructure lipid carrier, the drug content in the preparation process of the nanoparticles is improved, the drug encapsulation efficiency of the prepared progesterone nanostructure lipid carrier is reduced, but the drug loading capacity of the nanoparticles can be improved, and when the dosage reaches 20%, the drug loading capacity of the nanoparticles can reach 11.57%.

The invention discloses a combined package of an estradiol tablet and an estradiol didrogesterone tablet and a preparation method of the combined package. The package is composed of an estradiol tablet and an estradiol didrogesterone tablet. The combined package of the estradiol tablets and the estradiol digestrol tablets comprises the estradiol tablets and the estradiol digestrol tablets which are equal in tablet number, each of the estradiol tablets and the estradiol digestrol tablets comprises a tablet core and a coating layer, the tablet cores are prepared by a high-speed shearing granulation and tabletting process, and the prepared tablets are consistent with an originally developed agent Femoston in in-vitro release behavior, and have the advantages that the estradiol tablets and the estradiol digestrol tablets are combined, so that the estradiol and the estradiol digestrol tablets can be used for preparing the estradiol digestrol tablets; and in-vivo bioequivalence can be achieved. The high-speed shearing granulation mode is used for improving the particle mixing uniformity, so that the medicine content is more uniform, the in-vitro dissolution is stable, and the inter-batch difference is reduced. According to the invention, estradiol with a particle size of less than 20 [mu] m and didrogesterone with a particle size of less than 30 [mu] m are selected, high-speed shearing granulation is carried out by using a high stirring frequency, a special water adding device with a specific opening angle is selected, and the water adding amount, the water adding time and the stirring frequency are controlled at the same time, so that the tablets with rapid dissolution, uniform content and stable quality can be obtained.

The invention relates to the technical field of particle raw material stirring and mixing, in particular to a compound dibazol hydrochlorothiazide capsule raw material pretreatment stirring and mixing device which comprises a plurality of treatment frames which are evenly distributed from top to bottom and provided with upward openings, discharging openings are formed in the bottoms of the treatment frames, and stirring mechanisms are installed in the treatment frames; the device adopts a manner of matching layered laying and alternate stacking, active ingredients are independently stirred and flattened, then the active ingredients and auxiliary materials are stacked layer by layer, the active ingredients are uniformly attached to the surfaces of the auxiliary materials through throwing, and multi-stage gradual dilution is carried out, so that the problem that the active ingredients are easy to disperse and non-uniform when being directly mixed can be solved, the medicine content accuracy is improved, and the medicine quality is improved. And the components of each capsule are uniform and reach the standard.

The invention discloses timolol maleate gel emplastrum and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The gel paste comprises timolol maleate, a gel skeleton, a cross-linking agent, a cross-linking regulator, a filler, a penetration enhancer, a tackifier, a humectant, a pH regulator, a preservative and purified water. The preparation method comprises the following steps: preparing an oil phase; preparing the medicine and the water-soluble auxiliary materials into a solution; the tackifier adopts methyl acrylate / acrylic acid 2-ethylhexyl copolymer resin emulsion as a single phase; mixing the oil phase with the solution and the tackifier to obtain uniform gel paste with better ductility; and uniformly coating the paste on a backing layer, covering with a protective layer, and packaging to obtain the timolol maleate gel emplastrum. Through optimized prescription composition and process, the preparation has the characteristics of stable drug content and good skin adhesion, can realize continuous transdermal release of drugs, and is especially suitable for long-term safe treatment of infantile hemangioma.

The present invention discloses a method and device for predicting changes in the content of a drug in a living body. The present invention uses microsomes to construct a kinetic reaction system of a test substance in vitro, allowing the test substance to fully react in the microsomes, and determining the reaction conditions for conducting in vitro kinetic experiments using microsomes. Through the constructed microsomal reaction system, the metabolic rate of the test substance in the liver and / or small intestine of the living body is calculated, and its metabolic kinetic parameters are written into calculus equations using a computer, and then solved to finally obtain the kinetic process of the test substance, thereby making up for the shortcomings of conducting toxicity experiments using in vitro biological tissues. The present invention can analyze the toxicity characteristics of drugs in the liver of mice and predict the dose that produces liver toxicity without the need for animal experiments.

The invention belongs to the technical field of medical instruments, and particularly relates to a balloon dilatation catheter drug coating uniformity testing method and device.In the preset temperature environment, a balloon dilatation catheter is filled with liquid phase-change shaping filler, then the environment temperature is reduced to the testing temperature, and the uniformity of the balloon dilatation catheter drug coating is tested. According to the method, the phase change shaping filler is solidified and shaped in the balloon dilatation catheter, so that the solidified and shaped balloon dilatation catheter can be axially and / or radially cut at the test temperature to obtain a plurality of to-be-detected sample segments with regular shapes, and the area or length of each part of the to-be-detected sample segments can be conveniently calculated. Meanwhile, according to the type of the medicine attached to the balloon dilatation catheter, the content of the medicine on the sample segment to be detected is detected by utilizing a chemical analysis quantitative detection method, so that the measurement precision of the medicine content is effectively ensured; and evaluating the uniformity of the drug coating according to the area or length of each sample segment to be detected and the measured drug content.

According to the preparation method of the chlorogenic acid-methotrexate soluble microneedle, chondroitin sulfate and a methyl vinyl ether-maleic anhydride copolymer are adopted as matrix materials, and the drug-loaded microneedle is prepared through a two-step centrifugation method. The length of a needle body of the prepared microneedle is about 500 microns, the microneedle has good mechanical strength and skin puncture performance, the microneedle can be basically dissolved within 2 hours, the average drug content of chlorogenic acid is 57.97 + / -1.76 mu g / tablet, and the average drug content of methotrexate is 56.32 + / -1.67 mu g / tablet. An in-vitro percutaneous penetration test shows that the 6-hour cumulative transdermal rate of chlorogenic acid reaches 93.96%, the 6-hour cumulative transdermal rate of methotrexate reaches 86.92%, which are respectively 22.1 times and 3.0 times that of a control solution group, so that the efficient percutaneous delivery of the medicine is realized. The microneedle is small in skin irritation, the skin barrier can be naturally repaired within 15 minutes after puncture, and a new administration approach is provided for treatment of skin diseases such as psoriasis.

The invention discloses a method for verifying combination of a small molecule drug and a cell target protein, and belongs to the field of cytobiology and molecular biology. The method comprises the following steps: combining a small molecule drug with a cell target protein, and reducing the content of a free drug; the primary antibody is combined with cell protein to form a primary antibody complex; capturing a primary antibody complex by the PVDF membrane for incubating the secondary antibody; taking out the PVDF membrane, cleaning, and splitting miscellaneous protein in the solution to dissociate residual drugs; and detecting the amount of residual free drugs by HPLC, and analyzing data. The method solves the problem that small molecule-protein binding is difficult to directly detect in a traditional method, and the sensitivity is improved through combination of immunocapture and liquid chromatography or mass spectrometry quantitative detection. According to the method, a trace reagent system is adopted, the dosage of a single sample antibody is reduced by 70%, the PVDF membrane can be repeatedly used for 3-5 times, and the comprehensive detection cost is reduced by 60-80%. Various drug properties can be adapted (by adjusting lysis conditions such as pH / temperature).

The application provides a lurasidone orally disintegrating film composition, a preparation method and application thereof. The lurasidone orally disintegrating film composition comprises an active drug, a film-forming material, a plasticizer, an absorption promoter and a sweetening agent, and the active drug is 8-chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridyl)methyl]-4-piperidylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine as shown in formula I and / or a pharmaceutically acceptable salt thereof. The lurasidone orally disintegrating film composition has the advantages of good film-forming property, smooth surface, uniform color, no sand particle feeling, thin thickness, good taste, excellent mechanical property, stable property, no need of drinking water for instant dissolving in the oral cavity, fast oral absorption speed, simple process, high drug loading, good drug content uniformity and good market prospect.

The application relates to the technical field of atomizers, in particular to an atomizing device which comprises a cylinder body and a cover body, a separation sleeve, a liquid storage tank, a heater and an atomizing sheet, the liquid storage tank is fixed on the cover body, and a liquid outlet assembly is fixedly connected to the liquid storage tank. The liquid storage tank utilizes negative pressure to store liquid medicine in the liquid storage cavity, so that the liquid medicine in the liquid storage cavity is basically at a certain height during use. When the atomizing sheet is started, the atomized mist is overflowed from the rear liquid medicine through the upper film sheet, and then is discharged through the exhaust assembly, and in the process, since the height of the liquid medicine is basically constant, the drug content carried by the mist after passing through the liquid medicine is basically consistent, so that the stability of the drug content in the mist atomized by the atomizer is improved.

To provide granules with better uniformity of drug content by particle size than conventional granules, and to provide tablets containing the granules.SOLUTION: The granules of the present invention contain a drug (A), sugar alcohols (B), cellulose (C) having an angle of repose of less than 57°, and a binder (D). The content of the drug (A) preferably exceeds 1 mass% based on the total mass of the granules. The sugar alcohols (B) preferably have an average particle size D50 of less than 40 μm and an angle of repose of less than 65°. The loose bulk density of the cellulose (D) preferably exceeds 0.12 g / cm3. The tablet of the present invention contains the granules.SELECTED DRAWING: None

The invention relates to the field of quantitative control, in particular to an accurate quantitative intelligent control method and system for a pneumatic plastic regulating valve, and the method comprises the steps: collecting an upstream pressure sequence and a downstream pressure sequence; constructing a time window for the upstream pressure sequence, clustering the time window to obtain sub-segments, calculating a drug content accumulated value of all the sub-segments, and taking the last sub-segment as a quantitative ending segment in response to the fact that the drug content accumulated value is not less than a preset required drug content; calculating a first quantitative mark value, similarly obtaining a second quantitative mark value, and calculating the similarity between the first quantitative mark value and any second quantitative mark value to obtain a matching moment; and according to the calculated actual flow velocity, correcting the medicine-containing amount accumulated value to obtain a medicine-containing amount accumulated corrected value, and according to the medicine-containing amount accumulated corrected value, completing quantitative control. According to the technical scheme, the precision and efficiency of the quantitative control result can be improved.

The present invention discloses a kind of quinoline carboxylic acid ionic liquid W / O / W multiple emulsion and its preparation and application, belonging to the technical field of plant protection. In the present invention, dichloroquinoline carboxylic acid is used as the anion and jointly composes a functionalized ionic liquid with a structurally modified quaternary ammonium cation. The quinoline carboxylic acid ionic liquid can be prepared by an ion exchange reaction, an acid-base neutralization reaction or by extraction, and this kind of ionic liquid has high thermal stability. After preparing a W / O / W multiple emulsion with this ionic liquid as the active ingredient and emulsifier, the drug content can be controlled according to the drug release requirements; when this ionic liquid is applied to field weeding activities, compared with the application of conventional dichloroquinoline carboxylic acid agents, it can significantly improve the weeding activity of the agent, and thus can reduce the dosage of pesticides under the same weeding effect, having the effect of environmental protection.

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a mononitrate isosorbide oral dissolving film and a preparation method thereof. The mononitrate isosorbide oral dissolving film preparation is composed of a drug-containing layer and isolation layers which are compounded on the upper and lower surfaces of the drug-containing layer. The drug-containing layer comprises the following raw materials in percentage by mass: cyclodextrin-encapsulated mononitrate isosorbide 10-60%, film-forming material 20-80%, plasticizer 0-20% and auxiliary material 0-10%. The isolation layer comprises the following raw materials in percentage by mass: film-forming material 70-100%, plasticizer 0-30% and auxiliary material 0-10%. The mononitrate isosorbide oral dissolving film prepared by the application has the advantages of smooth appearance, good taste, uniform drug content, rapid dissolution under the action of saliva after entering the mouth, and further release and absorption, which greatly improves the drug administration compliance and solves the problem of surface crystallization of mononitrate isosorbide after long-term storage.