9 results about "Ramelteon" patented technology

This invention provides a sublingual film preparation comprising ramelteon, a film-forming material, and at least one or more of plasticizers, disintegrants, flavoring agents or sweeteners, and stabilizers, wherein the ramelteon is in an amorphous state, and a method for preparing the same. This invention is the first to develop ramelteon as a sublingual film preparation, thereby allowing ramelteon to be administered via the sublingual mucosa. Because the ramelteon of this invention exists in an amorphous state, it is absorbed more easily. The particle size of the ramelteon in the film preparation is dispersed at the molecular level, resulting in even better absorption. Furthermore, the drug does not easily aggregate and recrystallize, resulting in even better stability. However, it has relatively good solubility, so it can be completely dissolved in water within one minute and is rapidly absorbed by the oral mucosa, achieving the objective of rapid onset of action. The absolute bioavailability is significantly higher than tablets and general film preparations in previous studies (>30%), the onset of action is faster, there is no food interaction, the cost is low, and there are few side effects.

The present invention relates to a pharmaceutical composition comprising ramelteon and a nasal administration formulation. The pharmaceutical composition comprises ramelteon and polyethylene glycol. The pharmaceutical composition of the present invention has high stability and can be used to prepare a pharmaceutical formulation that meets the specifications for nasal administration formulations. Compared with oral tablets, the pharmaceutical composition of the present invention features improved bioavailability of ramelteon and a targeted concentration in brain tissue.

The invention discloses a ramelteon intermediate and a preparation method of ramelteon, and belongs to the technical field of medical chemistry. According to the preparation method, 1, 2, 6, 7-tetrahydro-8H-indeno [5, 4-b] furan-8-ketone is taken as an initial raw material, and three steps of reactions are carried out in sequence: 1) a Wittig-Horner reaction is carried out to generate an (E)-type olefinic nitrile intermediate; (2) carrying out asymmetric reduction on the alkene nitrile intermediate by adopting a Cu (II) / Walphos chiral ligand / reducing agent catalytic system to obtain an (S)-type nitrile intermediate with high selectivity; and 3) carrying out catalytic hydrogenation reduction on cyano groups in a continuous flow microreactor, and acidifying to obtain the ramelteon key intermediate with high optical purity. And carrying out propionylation and recrystallization on the intermediate to obtain the final product ramelteon. According to the method, the material loss of traditional chiral resolution is avoided, and the continuous flow hydrogenation technology remarkably improves the production safety and effectively controls the generation of byproducts.

A ramelteon sublingual film and a preparation method therefor. The sublingual film at least comprises ramelteon, a film forming material, and one or more of a plasticizer, a disintegrating agent, a flavoring agent or a sweetener, and a stabilizer, wherein the ramelteon is in an amorphous state. The ramelteon is developed into a sublingual film, such that the ramelteon can be administrated through sublingual mucosa. The ramelteon is present in an amorphous state and is thus easier to absorb; the particle size of the ramelteon in the film is molecular-level dispersion, such that the ramelteon can be absorbed better, drugs are not easy to gather and recrystallize, the stability is better, and the solubility is good; the ramelteon can be completely dissolved in water within 1 min and rapidly absorbed by oral mucosa, thereby achieving the objective of rapid onset of action; absolute bioavailability is greater than 30%, and the ramelteon sublingual film has obviously higher bioavailability than that of an original tablet and a common film, and has more rapid onset of action, no food effect, low costs, and less side effects.

The invention provides the stable ramelteon solution nasal spray, the medicine is atomized and then absorbed by the nasal mucosa to enter body fluid circulation, the problem of low bioavailability caused by the first-pass effect of the liver during oral administration of ramelteon is solved, meanwhile, the ramelteon solution nasal spray takes effect faster and is obviously superior to an oral preparation, the osmotic pressure conforms to the acceptable range of a human body, and the ramelteon solution nasal spray is free of irritation and has a good application prospect. The medicine is safer and is suitable for long-term treatment of chronic diseases. The ramelteon solution nasal spray provided by the invention is simple in preparation process, suitable for industrial production and low in production cost.

According to the stable ramelteon suspension nasal spray, medicine is atomized and then absorbed through nasal mucosa to enter body fluid circulation, the problem that the bioavailability is low due to the first-pass effect of the liver when ramelteon is orally taken is solved, meanwhile, the ramelteon suspension nasal spray takes effect faster and is obviously superior to an oral preparation, osmotic pressure conforms to the acceptable range of a human body, and the ramelteon suspension nasal spray is free of irritation and free of toxic and side effects. The medicine is safer and is suitable for long-term treatment of chronic diseases.

The invention relates to the field of stirring facilities, in particular to a ramelteon bulk drug production device which comprises a stirring box, a plate seat is fixedly mounted at the upper end of the stirring box, a reciprocating lead screw is rotatably mounted at the rear end of the plate seat, and a driving motor is fixedly mounted at the edge of the upper end of a base of the stirring box. The driving motor is connected with a stirring shaft of the stirring box, a speed reduction assembly is arranged between the reciprocating lead screw and the driving motor, a sliding block is arranged on the outer surface of the reciprocating lead screw, a guide rod is fixedly installed at the position, close to the upper portion of the reciprocating lead screw, of the rear end of the plate base, and a sliding sleeve is slidably installed on the outer surface of the guide rod. A feeding hopper is installed on the upper end face of the plate base in an attached mode, the sliding sleeve is fixed to the feeding hopper and the sliding block, and a storage hopper is fixedly installed above one end of the plate base. According to the invention, the use convenience is improved, the reaction is more stable, and the safety is ensured.

The invention discloses a core-coated tablet containing ramelteon and doxapine hydrochloride, which comprises the following active components: ramelteon and doxapine hydrochloride in a weight ratio of (4-8): 3.39, the core-coated tablet sequentially comprises a tablet core, a shell layer and a coating layer from inside to outside, the doxepin hydrochloride is located on the tablet core layer, the doxepin hydrochloride is located on the coating layer, and the shell layer is a sustained release layer. According to the invention, two active components are effectively isolated by preparing the compound core-coated sheet, and the release rate difference of the two drugs is solved by utilizing different drug release layers of the core-coated sheet, so that the physiological needs of rapid sleep induction and continuous sleep maintenance are realized.

The invention belongs to the technical field of biological medicines, and relates to application of ramelteon in preparation of a medicine for treating cardiovascular diseases. On the basis of the idea of new use of old drugs, 1912 drugs approved by FDA are used for high-throughput screening, and in combination with an in-vivo mouse model and an in-vitro cell model, it is found that ramelteon can strongly induce expression of Pgc1alpha and Pink1, and the mitochondrial homeostasis and the myocardial cell energy metabolism level are maintained. In-vivo experiments further prove that the ramelteon can relieve the development of cardiomyopathy induced by adriamycin and hypertrophic cardiomyopathy caused by aortic constriction and improve the development of heart failure, so that the ramelteon can improve the prognosis of cardiovascular diseases. The invention provides application of ramelteon as a mitochondrial energizer in preparation of drugs for treating cardiovascular diseases.