Drug delivery method and composition

Abstract

A drug delivery method and a composition. The drug delivery method comprises bringing an active ingredient in contact with an absorption enhancer containing a glucose polymer or a derivative thereof to form a mixture, and nasally administering the mixture. Further provided are a composition containing an active ingredient and a glucose polymer or a derivative thereof, and the use of the composition.

Description

A method and composition for delivering a drug Technical Field This disclosure pertains to the field of pharmaceutical technology and relates to a method and composition for delivering a drug, specifically a method and composition for nasal drug delivery. Background Technology Drugs targeting the central nervous system act on the brain and are typically administered systemically via intravenous or oral routes. However, the blood-brain barrier exists in the central nervous system, and only lipophilic, small-molecule substances can cross this barrier to reach the treatment site. Small molecules with high lipophilicity generally have poor solubility, making the development of intravenous formulations difficult. Even if oral administration is possible, it faces challenges such as oral absorption and the first-pass effect. Furthermore, developing intravenous or oral formulations requires significantly higher dosages to achieve effective therapeutic concentrations in the brain, leading to unnecessary systemic exposure and side effects. For example, propofol, a sedative, has high brain penetration but low solubility. Even when formulated into liposomal intravenous formulations, it may barely meet therapeutic needs, but excessive systemic exposure often causes liver damage. Dexmedetomidine, also a sedative, primarily causes hypotension and bradycardia due to systemic exposure. Bromocriptine, doxepin, fentanyl, and other drugs can all cause constipation with systemic exposure. Furthermore, most acute attacks of central nervous system diseases occur outside of hospitals, such as at home, workplace, or school, and often cannot be treated promptly. Many patients, especially young children and the elderly, have high requirements for medication adherence and need a fast-acting and conveniently administered drug to improve symptoms during acute attacks. Therefore, it is necessary to improve the administration methods or formulations of these drugs to increase treatment efficiency, reduce side effects, or improve drug safety. Brief description To address the aforementioned problems, in a first aspect, this disclosure provides a method for delivering an active ingredient via the nose or to cranial nerves, the brain, and / or the central nervous system, or via cranial nerves to the brain and / or the central nervous system, or preferentially to cranial nerves, the brain, and / or the central nervous system over the circulatory system, comprising contacting the active ingredient with an absorption enhancer containing a glucose polymer or a derivative thereof to form a mixture, and administering the mixture via the nose; wherein optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V. In a second aspect, this disclosure provides the use of glucose polymers or derivatives thereof as absorption enhancers in the preparation of nasally administered compositions, compositions delivered via cranial nerves, intracranial and / or central nervous system, or compositions delivered via cranial nerves to the intracranial and / or central nervous system, wherein optionally, the cranial nerves are selected from one or both of cranial nerve I and cranial nerve V, or optionally, the absorption enhancer does not contain any other absorption enhancers besides the glucose polymers or derivatives thereof; optionally, the composition contains an active ingredient. In a third aspect, this disclosure provides the use of a glucose polymer or a derivative thereof in the preparation of an absorption enhancer for use as an active ingredient administered nasally, for delivery of an active ingredient to cranial nerves, the brain and / or the central nervous system, or for delivery of an active ingredient to the brain and / or the central nervous system via cranial nerves, wherein optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V, or optionally, the absorption enhancer does not contain any other absorption enhancers besides the glucose polymer or a derivative thereof; optionally, the absorption enhancer contacts the active ingredient to form a composition. In a fourth aspect, this disclosure provides the use of antibacterial agents or antibacterial synergists containing glucose polymers or derivatives thereof in the preparation of compositions containing active ingredients. In a fifth aspect, this disclosure provides a composition for delivering an active ingredient via the nose or to cranial nerves, the brain, and / or the central nervous system, comprising: a) an active ingredient; and b) a glucose polymer or a derivative thereof; wherein the glucose polymer or derivative thereof serves as an absorption enhancer and / or an antibacterial agent or antibacterial synergist; optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V. In some aspects, the mixtures or compositions described in this disclosure do not contain any absorption enhancers other than the glucose polymers or their derivatives described above. In some aspects, the mixtures or compositions described in this disclosure do not contain any antibacterial agents or antibacterial synergists other than the glucose polymers or their derivatives described above. All active ingredients described in this disclosure are required to exert their effects on the central nervous system (particularly the brain). In other aspects, the aforementioned active ingredients are selected from one or more of the following: sumatriptan, zolmitriptan, dexmedetomidine, nalmefen, zavigepan, naloxone, diazepam, cocaine, midazolam, estaketone, dihydroergotamine, budesonide, fluticasone, bromocriptine, doxepin, fentanyl, propofol, nitrazepam, estazolam, oxazepam, zolpidem, triazolam, diazepam, and diazepam. Nitrodiazepoxide, Fludiazepoxide, Clonazepam, Buspirone, Fluvoxamine, Paroxetine, Trazodone, Mirtazapine, Chlorpromazine, Clozapine, Mefenamic acid, Olanzapine, Promethazine, Zaleplon, Alprazolam, Eszopiclone, Amitriptyline, Doxepin, Sertraline, Lorazepam, Clonazepam, Duspirone, Zopiclone, Propranolol, Citalopram, Escitalopram, Duloxetine, Venlazoline Faxine, Tramadol, Morphine, Pethidine, Codeine, Sufentanil, Carbamazepine, Sodium Valproate, Phenobarbital, Lamotrigine, Levetiracetam, Oxcarbazepine, Phenytoin Sodium, Primidone, Gabapentin, Topaz, Vigabatrin, Fluoxetine, Mipramine, Donepezil, Rosavirin, Galantamine, Memantine, Amantadine, Levodopa, Rotigotine, Rasagiline, Pramipexole Ropinirone, piribedil, rotigotine, trihexyphenidyl, tocapone, entacapone, buphenazine, atomoxetine, methylphenidate, amphetamine, quetiapine, perphenazine, sulpiride, aripiprazole, amisulpride, ziprasidone, buspirone, haloperidol, lurasidone, paliperidone, modafinil, telolide, and any pharmaceutically acceptable salt, solvate, or isomer thereof of any of the foregoing drugs. In some specific embodiments, the active ingredient is selected from one or more of dexmedetomidine, medetomidine, levodopa, or 7,8-dihydroxyflavone, and their pharmaceutically acceptable salts, solvates, or isomers thereof. In other aspects, the pharmaceutically acceptable salt is selected from one or more of propionate, hydrochloride, sulfate, nitrate, hydrobromide, hydroiodide, tartrate, formate, citrate, acetate, trichloroacetate, trifluoroacetate, gluconate, benzoate, lactate, fumarate, maleate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, and naphthalenesulfonate. In some specific embodiments, the pharmaceutically acceptable salt is selected from hydrochloride. In other aspects, the aforementioned glucose polymer or its derivative is selected from one or more of the following: dextran, α-glucan, oat β-glucan, fungal β-glucan, yeast β-glucan, seaweed β-glucan, icodextrin, polydextrose, starch, or derivatives of any of the foregoing. In other aspects, the aforementioned dextran is selected from one or more of dextran 10, dextran 20, dextran 40, dextran 60, dextran 70, and macromolecular dextran. In some specific embodiments, the aforementioned dextran is selected from dextran 5. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is at least 1%, preferably at least 2%, more preferably at least 5%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is from 1% to 20%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is from 1% to 10%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is from 1% to 5%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is from 2% to 20%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is from 2% to 10%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is from 2% to 5%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is selected from one of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, and about 13%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is 0.1% to 0.4%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is 0.4% to 2%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is 0.4% to 10%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is 0.1% to 20%. In other aspects, the weight-volume concentration of the above-mentioned dextran or its derivative is selected from about 0.1%, about 0.4%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 15%, or about 20%. In other respects, the aforementioned active ingredient is dexmedetomidine or its hydrochloride salt. In still other respects, the aforementioned absorption enhancer is dextran 70. In some aspects, the weight-volume concentration of the active ingredient described in this disclosure in a solution system such as a solution, mixture, nasal spray, or nasal drop is selected to be from 0.004% to 1.2%; in some specific embodiments, the weight-volume concentration of the active ingredient is selected to be from 0.02% to 0.12%; in some specific embodiments, the weight-volume concentration of the active ingredient is selected to be from 0.1% to 0.4%, for example, from 0.04% to 0.08%; in other specific embodiments, the weight-volume concentration of the active ingredient is selected to be about 0.007%, about 0.0087%, about 0.009%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.2%, about 0.3%, about 0.7%, and about 1%. In other aspects, the active ingredient is a therapeutically effective amount of dexmedetomidine, preferably with a weight-volume concentration of 0.004% to 1.2%. In other aspects, the weight-volume concentration of dexmedetomidine is selected from 0.02% to 0.12%. In other aspects, the weight-volume concentration of dexmedetomidine is selected from 0.1% to 0.4%, preferably from 0.04% to 0.08%. In other aspects, the weight-volume concentration of dexmedetomidine is selected from about 0.007%, about 0.0087%, about 0.009%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.2%, about 0.3%, about 0.7%, and about 1%. In other aspects, the mixture further comprises other pharmaceutical excipients selected from one or more of the following: antibacterial agents, pH adjusters, and osmotic pressure regulators; optionally, the antibacterial agent is selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol; optionally, the pH adjuster is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane; optionally, the osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol. In other aspects, the weight-volume concentration of the antibacterial agent is not greater than 0.05%, preferably not greater than 0.02%, more preferably not greater than 0.01%. In other aspects, the weight-volume concentration of the antibacterial agent is from 0.01% to 0.02%, preferably from 0.01% to 0.015%. In other aspects, the weight-volume concentration of the above-mentioned antibacterial agent is 0.005% to 0.02%, preferably 0.005% to 0.015%. In other aspects, the weight-volume concentration of the above-mentioned antibacterial agent is 0.005% to 0.01%. In other aspects, the weight-volume concentration of the above-mentioned antibacterial agent is selected from one of about 0.002%, about 0.003%, about 0.005%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.0125%, about 0.015%, and about 0.02%. In other aspects, the mixture has a pH of 7 or lower. In other aspects, the mixture has a pH of 5 to 7. In other aspects, the mixture has a pH of 5.5 to 7. In other aspects, the mixture has a pH of 5.5 to 6.5. In other respects, the above mixture has an osmotic pressure of 330 to 350 mOsm / kg. In still other respects, the above mixture is prepared as a nasal spray or nasal drops. In other respects, the use of glucose polymers or derivatives thereof in the preparation of the absorption enhancers described in this disclosure. In other respects, the above mixture has a brain tissue T-cell activity of no more than 15 minutes. max In other respects, the above mixture has a brain tissue T-cell activity of less than 10 minutes. max In other respects, the above mixture has a brain tissue T-cell activity of less than 5 minutes. max In other respects, the above mixture has a brain tissue T-cell activity of less than 3 minutes. max . In other respects, the AUC of brain tissue providing active ingredients in the absence of the aforementioned absorption enhancers... 0-t In comparison, the above mixture provides more of the corresponding brain tissue AUC. 0-t In other respects, the AUC of brain tissue providing the active ingredient in the absence of the aforementioned absorption enhancers... 0-t In comparison, the above mixture provides 1.1 times or more of the corresponding brain tissue AUC. 0-t In other respects, the AUC of brain tissue providing the active ingredient in the absence of the aforementioned absorption enhancers... 0-t In comparison, the above mixture provides 1.5 times or more of the corresponding brain tissue AUC. 0-t In other respects, the AUC of brain tissue providing the active ingredient in the absence of the aforementioned absorption enhancers... 0-t In comparison, the above mixture provides 3 times or more of the corresponding brain tissue AUC. 0-t . In other respects, among which brain tissue C provides the active ingredient in the absence of the aforementioned absorption enhancers... max In comparison, the above mixture provides 1.1 times or more of the corresponding brain tissue C. max For example, not less than 1.2 times, not less than 1.3 times, not less than 1.4 times, or not less than 1.5 times. In other aspects, C provides the active ingredient in the absence of the aforementioned absorption enhancers. max-脑组织 / C max-血浆 In comparison, the mixture provides 1.1 times or more of the corresponding C max-脑组织 / C max-血浆 For example, not less than 1.2 times, not less than 1.3 times, not less than 1.4 times, not less than 1.5 times, or not less than 2 times. In other respects, the AUC of the active ingredient provided in the absence of the aforementioned absorption enhancers... 0-t-脑组织 / AUC 0-t-血浆 In comparison, the aforementioned mixture provides 1.1 times or more of the corresponding AUC. 0-t-脑组织 / AUC 0-t-血浆For example, not less than 1.2 times, not less than 1.3 times, not less than 1.4 times, or not less than 1.5 times. The AUC described in this disclosure... 0-t-脑组织 / AUC 0-t-血浆 Indicates brain tissue AUC 0-t The value divided by the plasma AUC 0-t The numerical value of C. Similarly, the C described in this disclosure. max-脑组织 / C max-血浆 Indicates brain tissue C max The value divided by plasma C max The value. In other aspects, the above combination may further include pharmaceutical excipients, optionally selected from one or more of the following: antibacterial agents, pH adjusters, and osmotic pressure adjusters; optionally, the antibacterial agents may be selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol; optionally, the pH adjusters may be selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane; optionally, the osmotic pressure adjusters may be selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol. In other aspects, when the above-mentioned glucose polymer or its derivatives are used as antibacterial agents, the above combination may further include other pharmaceutical excipients. Optionally, the pharmaceutical excipients are selected from one or more of pH adjusters and / or osmotic pressure adjusters. Optionally, the pH adjuster is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane. Optionally, the osmotic pressure adjuster is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol. In other aspects, this disclosure provides formulations of the above-described compositions, the formulations being selected from nasal sprays or nasal drops. In other embodiments, the above-described compositions of this disclosure are used in the preparation of medicaments for treating diseases selected from those treated with sedation, hypnosis, anxiolytics, stress-reducing agents, anesthesia, analgesia, arousal agents, antidepressants, antiepileptics, anti-agitation agents, agitation inhibitors, treatments for insomnia, schizophrenia, acute transient psychotic disorders, schizoaffective disorders, schizophrenia, delusional disorders, depressive disorders, anxiety disorders, bipolar disorders, obsessive-compulsive disorder and related disorders, dissociative disorders, somatic discomfort or somatic experience disorders, Parkinson's disease, attention deficit hyperactivity disorder, tic disorders, mania, autism spectrum disorders, oppositional defiant disorder, intermittent rage disorder, substance use disorders, delirium, post-traumatic stress disorder, acute stress disorder, and adjustment disorders. These diseases all present with acute symptoms, requiring rapid onset of the medication to treat the acute symptoms and reduce harm to the patient during the acute phase. For example, patients with stress, agitation, agitation, mania, epilepsy, schizophrenia, bipolar disorder, acute transient psychotic disorder, schizoaffective disorder, schizotypal disorder, delusional disorder, dissociative disorder, somatic discomfort or somatic experience disorder, autism spectrum disorder, oppositional defiant disorder, intermittent explosive disorder, substance use disorder, delirium, post-traumatic stress disorder, acute stress disorder, and adjustment disorder often experience acute psychotic symptoms during an attack, including sudden and uncontrollable agitation, mania, and convulsions. These symptoms can easily cause harm to the patient or healthcare workers, and medication compliance is low during an attack, making medication administration difficult, and patients may hide or discard medication. After administration of the nasal delivery composition disclosed herein, the active ingredient can rapidly reach peak concentration in the target organ—the brain—leading to rapid onset of action, rapid relief of acute symptoms, and therapeutic effects. This allows the patient to quickly calm down, reducing the risk to themselves and healthcare workers, and also simplifying sequential therapy. In the treatment of patients with hypnosis, analgesia, insomnia, depression, anxiety, obsessive-compulsive disorder, autism spectrum disorder, and tic disorders, the nasal administration composition of this disclosure allows the active ingredient to rapidly reach peak concentration in the brain, resulting in a rapid onset of action and symptom relief. It also reduces anxiety caused by potentially uncontrollable symptoms. Furthermore, sedation, anesthesia, and arousal enhancement, commonly used in medical procedures, also rapidly reach peak brain concentration, providing a quick onset of action, alleviating patient anxiety, and improving patient comfort. In other embodiments, this disclosure provides a method for preparing the above-described composition, comprising contacting the various components of the composition. In other embodiments, this disclosure provides a device for intranasal drug delivery, wherein the device contains the composition described in this disclosure. In other embodiments, the intranasal drug delivery device of this disclosure is a metered dose device, wherein the metered dose device delivers a metered spray of the drug composition intranasally. Unconstrained by theoretical limitations, the inventors of this disclosure have surprisingly discovered that the dextran or its derivatives can promote the delivery of the active ingredient to or directly to the central nervous system via cranial nerves, particularly promoting the delivery of the active ingredient to cranial nerves I and V, or directly to the central nervous system via cranial nerves I and V. The inventors have also discovered that the dextran or its derivatives can also have antibacterial effects, thereby allowing for the elimination of conventional antibacterial agents such as benzalkonium chloride or a significant reduction in the dosage of conventional antibacterial agents. Detailed description To make the objectives, technical solutions, and advantages of this disclosure clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and are not intended to limit the scope of this disclosure in any way. The meanings of the terms used in this disclosure and claims are as follows. Other terms not explicitly stated herein are general terms in the art, unless otherwise specified. As used in this disclosure, dextran can be high molecular weight dextran, medium molecular weight dextran, low molecular weight dextran, small molecular weight dextran, or micro molecular weight dextran, depending on its molecular weight. In some implementations, the average molecular weight of high molecular weight dextran is 100,000 to 200,000, the average molecular weight of medium molecular weight dextran is 50,000 to less than 100,000, the average molecular weight of low molecular weight dextran is 30,000 to less than 50,000, the average molecular weight of small molecular weight dextran is 10,000 to less than 30,000, and the average molecular weight of micro molecular weight dextran is less than 10,000. In other embodiments, the average molecular weight of high molecular weight dextran is 100,000-200,000, the average molecular weight of medium molecular weight dextran is 50,000-80,000, the average molecular weight of low molecular weight dextran is 30,000-50,000, the average molecular weight of small molecular weight dextran is 10,000-20,000, and the average molecular weight of micro molecular weight dextran is below 10,000. In other embodiments, medium-molecular-weight dextran, such as dextran 70, has an average molecular weight of 64,000-76,000, and dextran 60 has an average molecular weight of 54,000-66,000; low-molecular-weight dextran, such as dextran 40, has an average molecular weight of 32,000-42,000; small-molecular-weight dextran, such as dextran 20, has an average molecular weight of 16,000-24,000; and micro-molecular-weight dextran, such as dextran 10, has an average molecular weight of less than 10,000. The “AUC” described in this disclosure 0-t "C" refers to the area under the curve from the start of drug administration to the last measurement point, where the drug concentration in the tissue is detected. max It measures the maximum drug concentration in tissues. T max The time it takes for the maximum drug concentration to be reached in the tissue. All numerical ranges in this disclosure include endpoint values. The term “about” as used in this disclosure means approximately or roughly. Generally, the term “about” is used herein to indicate that a numerical value varies by 10% above or below the provided value. For example, “about 40%” means within the range of 35%–45%. Numerical ranges in this document include all integers and fractions contained within that range (e.g., “1 to 5” includes 1, 1.5, 2, 2.75, 3, 3.90, 4, and 5). It should also be understood that all integers and fractions are considered to be modified by the term “about”. The term "and / or" as used in this disclosure refers to and covers any and all possible combinations of one or more of the associated listed items. When used in a list of two or more items, the term "and / or" means that any one of the listed items may be included alone, or may include any combination of two or more listed items. For example, if a group, combination, or composition is described as comprising (or containing) components A, B, C, and / or D, then the composition may contain A alone; contain B alone; contain C alone; contain D alone; contain a combination of A and B; contain a combination of A and C; contain a combination of A and D; contain a combination of B and C; contain a combination of B and D; contain a combination of C and D; contain a combination of A, B, and C; contain a combination of A, B, and D; contain a combination of A, C, and D; contain a combination of B, C, and D; or contain a combination of A, B, C, and D. The term "pharmaceutically acceptable salt" as used in this disclosure refers to a salt obtained by reacting an active ingredient (or "compound") with a pharmaceutically acceptable (relatively non-toxic, safe, and suitable for patient use) acid or base. When a compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the free form of the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium, potassium, calcium, aluminum, magnesium, bismuth, and ammonium salts. When a compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the free form of the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloride, sulfate, and methanesulfonate salts. The "absorption enhancer" described in this disclosure refers to an agent that can improve the efficiency of intranasal administration of an active ingredient into the brain, for example, by increasing the C60 concentration in brain tissue or cranial nerves. max AUC, C max-脑组织 / C max-血浆 and AUC 0-t-脑组织 / AUC 0-t-血浆 One or more of the following, and / or a decrease in T in brain tissue max The value of (h) enhances the efficacy of nasal administration for treating central nervous system diseases. The absorption enhancer described in this disclosure can be formulated into a nasal dosage form with the active ingredient and other pharmaceutical excipients. The absorption enhancer described in this disclosure promotes the delivery of the nasally administered active ingredient to the brain and / or central nervous system via cranial nerves, wherein the cranial nerves are selected from one or both of cranial nerve I and cranial nerve V. In some embodiments, the absorption enhancer does not contain any absorption enhancers other than the glucose polymer or its derivatives. In some embodiments, the glucose polymer or its derivatives are selected from one or more of the following: dextran, α-glucan, oat β-glucan, fungal β-glucan, yeast β-glucan, seaweed β-glucan, icodextrin, polydextrose, starch, or derivatives of any of the foregoing. In some specific embodiments, the absorption enhancer is selected from dextran or its derivatives. In other embodiments, the absorption enhancer is selected from one or more of dextran 10, dextran 20, dextran 40, dextran 60, dextran 70, macromolecular dextran, or derivatives thereof. The term "pharmaceutical composition" as used in this disclosure refers to one or more of the pharmaceutically active ingredients of this application or pharmaceutically acceptable salts thereof, mixed with pharmaceutical excipients. The purpose of a pharmaceutical composition is to facilitate the administration of the active ingredient to a living organism. The pharmaceutical excipients may be pharmaceutically acceptable carriers and excipients. The "antimicrobial agents" described in this disclosure, also known as preservatives, are chemical substances that can inhibit the growth of microorganisms. The inhibitory effect of antimicrobial agents on microorganisms is achieved by affecting cellular substructures, including the cell wall, cell membrane, protein synthesis system, metabolic enzymes, and genetic material. Antimicrobial agents can be selected from acids, alcohols, quaternary ammonium salts, parabens, and organomercuric compounds. Any antimicrobial agent that enables the solution, mixture, nasal spray, or nasal drop formulations described in this disclosure to achieve the pharmaceutically required antimicrobial efficacy and meet the needs of drug development is applicable in this disclosure. In some specific embodiments, the aforementioned antimicrobial agents are selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol. In other specific embodiments, dextran acts as an antimicrobial synergist, working synergistically with a reduced dosage of the aforementioned antimicrobial agents to achieve antimicrobial efficacy. In still other specific embodiments, dextran is used as the sole antimicrobial agent in the solution system described in this disclosure to achieve antimicrobial efficacy. The "pH adjuster" described in this disclosure is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane. Any pH adjuster that can adjust the pH of a mixture to meet the pH requirements for drug development is applicable. The pH value of a healthy nasal cavity is usually in the weakly acidic range of 5.5-6.5. In some specific experimental procedures, the pH adjuster adjusts the pH value of the solution system, mixture, nasal spray, or nasal drop described in this disclosure to 5.5-6.5. The "osmotic pressure regulator" described in this disclosure is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol. Any osmotic pressure regulator that can adjust the osmotic pressure of the mixture to meet the requirements of drug development is applicable. The term "treatment" as used in this disclosure refers to the application of an effective amount of the active ingredient of this application to an individual to alleviate symptoms or complications, delay disease progression, inhibit disease progression, reduce or alleviate symptoms and complications, and / or cure or eliminate disease or condition, as well as prevent disease. Prevention is understood to mean the application of the active ingredient of this application to an individual for the purpose of combating disease or condition to prevent the onset of symptoms or complications. In one embodiment, "treatment" means the application of an effective amount of the active ingredient described in this disclosure for the purpose of reducing, improving, preventing, or eradicating (curing) symptoms or disease states. The terms “effective amount,” “therapeutic effective amount,” or “therapeutic effective dose” used in this disclosure refer to the amount of the active ingredient described in this disclosure that is capable of evoking a biological or medical response in an individual (e.g., improving symptoms, alleviating symptoms, slowing or delaying disease progression, or preventing disease). The “effective dose” of this disclosure may vary depending on the patient’s age, sex, and weight, and is generally in the range of 0.1-1000 mg / kg body weight, such as 1-100 mg / kg body weight, 50-100 mg / kg body weight. However, because it may increase or decrease depending on the route of administration, disease severity, sex, weight, age, health status, time of administration, frequency of administration, etc., the dose is not limited in any way to the scope of this disclosure. This dose may be administered during disease flare-ups, and the frequency of administration may be once daily or more, such as any of 2, 3, 4, 5, or more than 5 times daily. This dose may be administered once weekly or more frequently. This dose may be intermittent (e.g., once daily for 7 days, followed by 7 days without a dose, repeated for any 14-day period, such as 2 months, 4 months, 6 months, or longer). This dose may be continuous (e.g., once weekly for several weeks). The term "target of administration" in this disclosure includes, but is not limited to, mammals. As used herein, the term "mammal" includes, but is not limited to, primates (e.g., apes and humans), non-human primates (e.g., monkeys, baboons, chimpanzees, gorillas), cattle, sheep, goats, ungulates, pigs, horses, cats, dogs, rabbits, pinnipeds, rodents (e.g., rats, cheek rats, and mice), etc. In some embodiments of this disclosure, the individual is a human being. Human individuals include individuals of all ages, both male and female, including newborns, infants, adolescents, teenagers, adults, and the elderly. Intranasal administration of the pharmaceutical compositions disclosed herein can be achieved by any known method. In specific embodiments, intranasal administration is by inhalation (e.g., using an inhaler, nebulizer, or spray device), optionally via a nebulizer, tubing, infusion tube, syringe, dropper, pipette, gauze, etc. As further illustrated, the pharmaceutical compositions can be prepared as the following intranasal administration formulations: (1) nasal drops, (2) powder or liquid sprays or aerosols, (3) liquid or semi-solid via swabs, gauze, or other similar means of application, (4) gels, creams, or ointments, or by any means currently known or subsequently developed in the art. In specific embodiments, the method of administration is by nasal drops, nasal sprays, or aerosols. As used herein, aerosols can be used to deliver powders, liquids, or dispersions (solids in a liquid). Intranasal administration of the pharmaceutical composition disclosed herein can be achieved by any known device. In specific embodiments, intranasal administration is achieved by using an inhaler, nebulizer, or spray device, optionally via a nebulizer, tubing, infusion tubing, syringe, drip instillation device, pipette, gauze, etc. The “metered dose device” mentioned in this disclosure refers to a device that provides a specified dose. Specific Implementation All concentrations in this prescription are weight-volume concentrations. For example, if 10 ml of dexmedetomidine nasal solution contains 1 mg of benzalkonium chloride, the weight-volume concentration of benzalkonium chloride is expressed as 0.01% (w / v). In this disclosed formulation, the weight / volume concentration of dexmedetomidine hydrochloride is calculated based on dexmedetomidine. For example, a dexmedetomidine hydrochloride concentration of 0.8 mg / ml in the formulation means that each milliliter of solution contains 0.8 mg of dexmedetomidine. The conversion factor between dexmedetomidine hydrochloride and dexmedetomidine is 1.182. " / " indicates that the corresponding formulation does not contain this substance. The SD rat disclosed herein is the Sprague Dawley rat. N / A: Not Applicable, meaning it is not applicable here. Table 1 Laboratory Animals and Instruments Used Example 1: Preparation of Formula 1 Solution Prescription 1: Dexmedetomidine hydrochloride 10 mg / ml, sodium chloride 0.9% (w / v), benzalkonium chloride 0.02% (w / v), dextran 70 10% (w / v). 11.82 g of dexmedetomidine hydrochloride, 9 g of sodium chloride, 0.2 g of benzalkonium chloride, and 100 g of dextran 70 were added to approximately 800 ml of purified water and stirred to dissolve. The pH was adjusted to 5.5-6.5 with 0.1 M sodium hydroxide solution, and purified water was added to a final volume of 1 L. The solution was then filtered through a 0.2 μm polyethersulfone or cellulose membrane to obtain the solution specified in Formula 1. Example 2: Exposure of SD rats after nasal administration of Formula 1 solution into brain nerves and plasma via nasal absorption. Nasal administration: Three groups of SD rats were established, with nine rats in each group. Each group was administered Formula 1 solution nasally at a dose of 50 μg / kg (calculated as dexmedetomidine). All SD rats had free access to food and water after administration. Plasma, cranial nerve I, and cranial nerve V were collected at 5 min, 15 min, and 30 min after administration, with 2-3 rats per time point. Sample processing: Whole blood was anticoagulated with EDTA-K2. Within 30 minutes of collection, the blood was centrifuged at 3000g for 10 minutes at 2-8℃. After centrifugation, the separated plasma was transferred to a new 1.5mL centrifuge tube and stored at -80℃. Cranial nerve I and Cranial nerve V samples were collected and stored in 2mL cryovials at -80℃. Analytical methods: The concentrations of dexmedetomidine in rat plasma and cranial nerves were detected using LC-MS / MS with a Shimadzu LC30AD and AB Sciex QTRAP 5500 instrument. Pharmacokinetic parameters and tissue distribution after intranasal administration were calculated. The experimental results are shown in Table 2. Table 2. Exposure of SD rats to brain nerves and plasma after nasal administration of Formula 1 solution via nasal droplets. The experimental results show that after SD rats received intranasal administration of Formula 1 solution, the C-cell activity of cranial nerves I and V, which were treated with Formula 1 solution, was reduced. max AUC 0-t and AUC 0-t-组织 / AUC 0-t-血浆 The value is relatively large, and the plasma C max and AUC 0-t The levels are significantly lower. This indicates that the drug exposure in cranial nerves I and V after administration of Formula 1 solution is significantly higher, while the plasma exposure is significantly lower, demonstrating that Formula 1 solution of this disclosure has strong tissue targeting. In SD rats, after intranasal administration of Formula 1 solution, the exposure of dexmedetomidine in cranial nerves I and V was significantly higher than that in plasma. Cranial nerve I and V pathways are considered the primary routes of drug delivery to the brain via the nose. Nasal administration of Formula 1 solution of this disclosure avoids drug degradation due to gastric acid, bile, digestive enzymes, and other first-pass effects, and also reduces the dosage and side effects. Example 3: Investigation of Absorption Enhancer Dosage Dextran 70 was used as an absorption enhancer for nasal administration solutions. The formulation design is shown in Table 3. The effect of different concentrations of dextran 70 on the brain absorption efficiency of the active ingredient in the solution was investigated. Table 3 shows the prescriptions used to investigate the dosage of different absorption enhancers. Preparation of solutions for prescriptions 2 to 8: Dextran 70 solutions of different concentrations were prepared using physiological saline, with concentrations of 0%, 0.1%, 0.4%, 2%, 10%, 15%, and 20% (100 ml each). Then, 95 mg of dexmedetomidine hydrochloride was dissolved in each of the prepared solutions to obtain solutions for prescriptions 2 to 8. The liquid parameter characterization data for solutions 2 to 8 are shown in Table 4. Table 4 Characterization of liquid parameters for solutions of formulations 2 to 8: viscosity & angularity Conclusion: The solutions of formulations 2 to 8 have viscosity values ​​between 0 and 30 mPa·s, and are all liquid formulations suitable for nasal spray atomization. This is because appropriate viscosity can provide resistance during the press-to-spray operation, which is conducive to the uniform formation of atomized droplets. Example 4: Pharmacokinetic behavior of solutions from formulations 2 to 8 in vivo Nasal administration: 21 groups of SD rats were established, with 12 rats in each group. The rats were administered solutions of formulations 2 to 8 prepared in Example 3 via nasal instillation. The dosage, calculated as dexmedetomidine, was 16 μg / kg. All SD rats had free access to food and water after administration. Brain nerve I, brain nerve V, olfactory bulb, brain tissue, and plasma were collected at 5 min, 15 min, 30 min, and 1 h post-administration, with 3 SD rats at each time point. Sample processing: Whole blood was anticoagulated with EDTA-K2. Within 30 minutes of collection, the blood was centrifuged at 3000g for 10 minutes at 2-8℃. After centrifugation, the separated plasma was transferred to a new 1.5mL centrifuge tube and stored at -80℃. Cranial nerve I, cranial nerve V, olfactory bulb, and brain tissue were collected and stored in 2mL cryovials at -80℃. Analytical methods: Using a Shimadzu LC30AD and AB Sciex QTRAP 5500 instrument, LC-MS / MS was employed to detect the concentrations of dexmedetomidine in cranial nerve I, cranial nerve V, olfactory bulb, brain tissue, and plasma of SD rats. Relevant pharmacokinetic parameters and tissue distribution after intranasal administration were calculated. The experimental results are shown in Table 5. Table 5. Pharmacokinetic parameters and tissue distribution of intranasally administered solutions of formulations 2 to 8 in SD rats. The results showed that the presence of dextran 70 in the formulation could improve the efficiency of the active ingredient's entry into the brain. For example, it could increase the C60 concentration in brain tissue or cranial nerves. max And AUC, and C max-脑组织 / C max-血浆 and AUC 0-t-脑组织 / AUC 0-t-血浆 One or more of the following, and / or reduce T max The value of (h). For example, when the prescription contains 0.1%-0.4% dextran 70, it can increase the C... max-脑组织 / C max-血浆 The ratio of AUC 0-t-脑组织 / AUC 0-t-血浆 The values ​​indicate that 0.1%-0.4% dextran 70 can increase the proportion of the active ingredient delivered to the brain via intranasal administration; when the formulation contains 0.4%-2% dextran 70, it can shorten the T3-weighted plasma concentration in rat brain tissue. max (h) Increase C in rat brain tissue max and C max-脑组织 / C max-血浆 The value. When the prescription contains 0.4%-10% dextran 70, it can increase the C value of brain tissue. max The value and C max-脑组织 / Cmax-血浆 The value; when the prescription contains 0.1%-20% dextran 70, it can increase the C value in rats. max-脑组织 / C max-血浆 The value of . Example 5: Evaluation of the effects of dextran of different molecular weights as absorption enhancers Dextran 5, dextran 10, and dextran 20 were used as absorption enhancers for nasal administration solutions, and the formulation design is shown in Table 6. The effects of different molecular weights of dextran on the brain absorption efficiency of the active ingredients in the solution were investigated. Table 6. Formulations of dextran of different molecular weights as absorption enhancers Preparation of solutions of prescriptions 9 to 11: Prepare a 0.8 mg / ml dexmedetomidine solution with physiological saline. Take three 100 ml portions of the prepared dexmedetomidine solution and dissolve 2 g of dextran 5, 2 g of dextran 10, and 2 g of dextran 20 in each portion to prepare solutions of prescriptions 9 to 11. Example 6: In vivo pharmacokinetic behavior of solutions of formulations 9 to 11 The pharmacokinetic behavior of solutions of formulations 9 to 11 in vivo was investigated using the experimental method described in Example 4. The results are shown in Table 7. Table 7. Pharmacokinetic parameters and tissue distribution of intranasally administered solutions of formulations 9 to 11 in SD rats. Comparison of pharmacokinetic parameters and tissue distribution results of solutions from formulations 9 to 11 with those from formulation 2 showed that the presence of dextran 5, dextran 10, or dextran 20 in the formulation can improve the efficiency of the active ingredient entering the brain. For example, it can increase C... max-脑组织 / C max-血浆 The value of . The pharmacokinetic parameters and tissue distribution results of solutions from prescriptions 2 to 11 show that dextran 70, dextran 20, dextran 10, and dextran 5 can all enhance the efficiency of nasal delivery of the active ingredient dexmedetomidine into the brain. This further demonstrates that dextran of various molecular weights, including medium-molecular-weight, low-molecular-weight, small-molecular-weight, and micro-molecular-weight dextran, can all enhance the efficiency of nasal delivery of the active ingredient dexmedetomidine into the brain. Example 7 investigated the effect of antibacterial agents on the efficiency of dextran 70 as an absorption enhancer in promoting the brain absorption of active ingredients. To investigate the effect of dextran 70 as an absorption enhancer on the brain absorption efficiency of the active ingredient when a conventional antibacterial agent is present in the solution, formulation 12 was designed. Formulation 12 consists of: dexmedetomidine 0.8 mg / ml, dextran 70 2% (w / v), benzalkonium chloride 0.02% (w / v), and sodium chloride 0.9% (w / v). Preparation of Formula 12 solution: Weigh 95 mg dexmedetomidine hydrochloride, 2000 mg dextran 70, 20 mg benzalkonium chloride, and 900 mg sodium chloride for later use. Mix the weighed materials with 90 ml of purified water and dissolve them. Adjust the pH value to 6.0 ± 0.5 with 1 M sodium hydroxide solution. Add purified water to 100 ml to prepare the Formula 12 solution. Example 8: Pharmacokinetic behavior of the solution of formulation 12 in vivo The pharmacokinetic behavior of the solution of formulation 12 was investigated in vivo using the experimental method described in Example 4. The results are shown in Table 8. Table 8. Pharmacokinetic parameters and tissue distribution of Formula 12 solution administered intranasally to SD rats. Formula 5 consists of dexmedetomidine 0.8 mg / ml, dextran 702% (w / v), and sodium chloride 0.9% (w / v). Furthermore, the pharmacokinetic parameters and tissue distribution results of Formula 5 compared to Formula 2 in Example 4 indicate that Formula 5 has a higher C-value in brain tissue. max and C max-脑组织 / C max-血浆 All were significantly improved, and brain tissue T max The significant decrease in (h) indicates that dextran 70 in prescription 5, as an absorption enhancer, has the effect of improving the efficiency of the active ingredient entering the brain via the nose. Formula 12, based on Formula 5, increases the usual dosage of the conventional antibacterial agent benzalkonium chloride and adjusts the pH to 6.0 ± 0.5, which is within the usual pH range for nasal administration solutions. Pharmacokinetic parameters and tissue distribution in SD rats administered nasally with Formula 12 compared to Formula 5 show that when the nasal administration solution contains both the absorption enhancer described in this disclosure (e.g., dextran 70) and the usual dosage of a conventional antibacterial agent (e.g., 0.02% w / v benzalkonium chloride), and the pH of the solvent is adjusted to the pH of a conventional nasal administration solution, the absorption enhancer described in this disclosure still has the effect of improving the efficiency of the active ingredient entering the brain via the nose. Example 9: Investigation of the brain absorption efficiency of dextran 70 as an absorption enhancer. The effect of using dextran 70 as an absorption enhancer in nasal administration solution on the brain absorption efficiency of other active ingredients was investigated. The formulation design is shown in Table 9. Table 9 shows the formulation of dextran 70 as an absorption enhancer and other active ingredients. Preparation of solutions of prescription 13 and prescription 15: Prepare two 100ml portions of 2% dextran 70 solution with physiological saline, and dissolve 100mg of 7,8-dihydroxyflavone and 16g of levodopa in each portion to obtain solutions of prescription 13 and prescription 15. Preparation of solutions of prescription 14 and prescription 16: Prepare two 100ml solutions of physiological saline containing 0.02% benzalkonium chloride and 2% dextran 70. Dissolve 100mg of 7,8-dihydroxyflavone and 16g of levodopa in each solution to obtain solutions of prescription 14 and prescription 16. Example 10: In vivo pharmacokinetic behavior of solutions from formulations 13 to 16 The pharmacokinetic behavior of solutions of formulations 13 to 16 was investigated in vivo, following the experimental method described in Example 4. The difference was that the dosage of formulations 13 and 14 was 20 μg / kg, and olfactory nerve, trigeminal nerve, brain tissue, and plasma were collected at 5 min, 15 min, and 30 min after administration; the dosage of formulations 15 and 16 was 3.2 mg / kg, and olfactory nerve, trigeminal nerve, brain tissue, and plasma were collected at 15 min and 30 min after administration. The results are shown in Tables 10 and 11. Table 10 Pharmacokinetic parameters and tissue distribution of SD rats administered intranasally with formulations 13 and 14. Table 11 Pharmacokinetic parameters and tissue distribution of SD rats administered intranasally with formulations 15 and 16. As shown in Table 10, the absorption enhancer dextran 70 can increase C in brain tissue. max and AUC 0-t , and C max-脑组织 / C max- 血浆 and AUC 0-t-脑组织 / AUC 0-t-血浆 The value of [value missing] significantly improves the brain absorption efficiency of the active ingredient 7,8-dihydroxyflavone. As shown in Table 11, the absorption enhancer dextran 70 can increase the C [value missing] in brain tissue. max and AUC 0-t It has the effect of significantly improving the efficiency of the active ingredient levodopa entering the brain. Example 11 examines the antibacterial efficacy of dextran as an antibacterial agent or antibacterial promoter. Chinese Patent Application CN118217243A (publication date: June 21, 2024) Specification No.

[0040] The text states: "When the concentration of BKC (benzalkonium chloride) is low, especially below 0.01%, its inhibitory efficacy against Escherichia coli is unstable and cannot guarantee stable compliance with relevant standards." 11.1 Formulation Design: To investigate the antibacterial efficacy of dextran as an antibacterial agent or antibacterial promoter, the formulation design is shown in Table 12. Table 12 shows formulations examining the antibacterial efficacy of dextran as an antibacterial agent or antibacterial promoter. Note: (1) The weight-volume concentration of dexmedetomidine hydrochloride is expressed as dexmedetomidine; (2) Benzalkonium chloride is expressed as nC. 12 H 25 and nC 14 H 29 The total amount of homologous series is calculated and then converted to dry weight. Solutions of formulations 17 to 22 were prepared according to the preparation method of Example 1. 11.2 Antibacterial efficacy test According to the provisions of General Chapter 1121 [Test Method for Antibacterial Efficacy] in Part III of the 2020 edition of the Chinese Pharmacopoeia, the antibacterial efficacy tests of solutions of prescriptions 17 to 22 against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger were conducted. The criteria for judging the antibacterial efficacy of nasal preparations are shown in Table 13. The test results of the antibacterial effects of prescriptions 17 to 22 are shown in Table 14. Table 13 Criteria for Judging the Antibacterial Efficacy of Nasal Preparations Note: NI not increased means that the number of experimental bacteria increased by no more than 0.5lg compared to the previous measurement time. Table 14 Results of antibacterial efficacy experiments for prescriptions 17 to 22 The results showed that adding an appropriate amount of dextran to the formulation of dexmedetomidine nasal spray could significantly reduce the dosage of conventional antibacterial agents (such as benzalkonium chloride) or eliminate the need for conventional antibacterial agents, while still meeting the requirements for antibacterial efficacy, indicating that dextran has antibacterial and / or synergistic antibacterial effects. Higher concentrations of benzalkonium chloride can affect the function of nasal mucosal cilia movement, causing irritation and discomfort for patients, thus reducing patient tolerance. The nasal administration formulation disclosed herein, using 2% to 10% dextran, can meet antibacterial standards without the use of other antibacterial agents, or by reducing the benzalkonium chloride content without introducing other antibacterial agents, demonstrating unexpected effectiveness. As can be seen from Examples 1 to 11, the use of 2% to 10% dextran 70 in nasal drug delivery solutions can act as an absorption enhancer to improve the efficiency of active ingredients entering the brain, and also has antibacterial or synergistic antibacterial effects, resulting in unexpected benefits. Example 12: Sleep-promoting effect of a prescription solution of dextran 70 in SD rats. Eighteen male SD rats were randomly and equally divided into six groups, with three SD rats in each group. Three groups of SD rats received intranasal administration of Formula 2 solution without dextran 70, with doses of 10 μg / kg (low dose), 25 μg / kg (medium dose), and 50 μg / kg (high dose) of dexmedetomidine, respectively. The other three groups of SD rats received intranasal administration of Formula 5 solution containing dextran 70, with doses of 10 μg / kg, 25 μg / kg, and 50 μg / kg of dexmedetomidine, respectively. After intranasal administration, each SD rat's open field activity was recorded and analyzed for 30 minutes. The activity trajectory, speed, and time spent at rest of each SD rat in the open field were automatically tracked and analyzed in real time by software. Experimental results showed that SD rats receiving Formula 2 solution via intranasal administration had a slower onset of action compared to those receiving Formula 5 solution via intranasal administration. The onset dose of Formula 5 solution (containing dextran 70) in SD rats via intranasal administration was also lower than that of Formula 2 solution (without dextran 70), which could reduce the dosage and improve the efficacy and safety of the therapeutic agent in practical applications. This disclosure is not limited to the optional embodiments described above, and anyone can derive other various forms of products based on the teachings of this disclosure. The specific embodiments described above should not be construed as limiting the scope of protection of this disclosure, which should be determined by the claims, and the description can be used to interpret the claims.

Claims

1. A method for delivering an active ingredient via nasal delivery or delivery of an active ingredient to cranial nerves, the brain, and / or the central nervous system, or delivery of an active ingredient via cranial nerves to the brain and / or the central nervous system, or delivery of an active ingredient preferentially to cranial nerves, the brain, and / or the central nervous system relative to delivery to the circulatory system, the method comprising: The active ingredient is contacted with an absorption enhancer containing a glucose polymer or a derivative thereof to form a mixture, and the mixture is administered nasally; wherein, optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V.

2. The method according to claim 1, wherein, The absorption enhancer does not contain any other absorption enhancers besides the glucose polymer or its derivatives.

3. The method according to claim 1 or 2, wherein, The active ingredient is selected from one or more of the following: sumatriptan, zolmitriptan, dexmedetomidine, nalmefen, zavigepan, naloxone, diazepam, cocaine, midazolam, estaketone, dihydroergotamine, budesonide, fluticasone, bromocriptine, doxepin, fentanyl, propofol, nitrazepam, estazolam, oxazepam, zolpidem, triazolam, diazepam, nitrazepam. Fluazinam, clonazepam, buspirone, fluvoxamine, paroxetine, trazodone, mirtazapine, chlorpromazine, clozapine, mirtazapine, olanzapine, promethazine, zaleplon, alprazolam, eszopiclone, amitriptyline, doxepin, sertraline, lorazepam, clonazepam, duspironone, zopiclone, propranolol, citalopram, escitalopram, duloxetine, venlafaxine, Tramadol, morphine, meperidine, codeine, sufentanil, carbamazepine, sodium valproate, phenobarbital, lamotrigine, levetiracetam, oxcarbazepine, phenytoin sodium, primidone, gabapentin, tocopherol, vigabatrin, fluoxetine, mirtamine, donepezil, rivastigmine, galantamine, memantine, amantadine, levodopa, rotigotine, rasagiline, pramipexole, ropinirole, piribedil, rotigotine, trihexyphenidyl, tocapone, entacapone, buphenazine, atomoxetine, methylphenidate, amphetamine, quetiapine, perphenazine, sulpiride, aripiprazole, amisulpride, ziprasidone, buspirone, haloperidol, lurasidone, paliperidone, modafinil, telolide, any pharmaceutically acceptable salt, solvate, or isomer of any of the foregoing drugs.

4. The method according to claim 1 or 2, wherein, The active ingredient is selected from 7,8-dihydroxyflavone and its pharmaceutically acceptable salts, solvates or isomers thereof.

5. The method according to claim 3 or 4, wherein, The pharmaceutically acceptable salt is selected from one or more of the following: propionate, hydrochloride, sulfate, nitrate, hydrobromide, hydroiodide, tartrate, formate, citrate, acetate, trichloroacetate, trifluoroacetate, gluconate, benzoate, lactate, fumarate, maleate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, and naphthalenesulfonate.

6. The method according to any one of claims 1 to 5, wherein, The glucose polymer or its derivatives are selected from one or more of the following: dextran, α-glucan, oat β-glucan, fungal β-glucan, yeast β-glucan, seaweed β-glucan, icodextrin, polydextrose, starch, or derivatives of any of the foregoing.

7. The method according to claim 6, wherein, The dextran is selected from one or more of dextran 10, dextran 20, dextran 40, dextran 60, dextran 70 and macromolecular dextran.

8. The method according to claim 6, wherein, The dextran mentioned is selected from dextran 5.

9. The method according to claim 6, wherein, The dextran or its derivative has a weight-volume concentration of at least 1%, for example at least 2%, and even more specifically at least 5%.

10. The method according to any one of claims 6 to 9, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 20%.

11. The method according to any one of claims 6 to 10, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 10%.

12. The method according to any one of claims 6 to 11, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 5%.

13. The method according to any one of claims 6 to 10, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 20%.

14. The method according to any one of claims 6 to 10, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 10%.

15. The method according to any one of claims 6 to 10, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 5%.

16. The method according to any one of claims 6 to 10, wherein, The weight-volume concentration of the dextran or its derivative is selected from one of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, and about 13%.

17. The method according to any one of claims 6 to 8, wherein, The weight-volume concentration of the dextran or its derivative is selected from 0.1% to 0.4%, 0.4% to 2%, 0.4% to 10%, and / or 0.1% to 20%.

18. The method according to any one of claims 1 to 17, wherein, The active ingredient is dexmedetomidine or its hydrochloride salt.

19. The method according to any one of claims 1 to 18, wherein, The absorption enhancer is dextran 70.

20. The method according to any one of claims 1 to 19, wherein, The active ingredient is a therapeutically effective amount of dexmedetomidine, for example, the weight-volume concentration of dexmedetomidine is selected to be 0.004% to 1.2%.

21. The method according to any one of claims 1 to 20, wherein, The weight-volume concentration of the active ingredient is selected to be between 0.02% and 0.12%.

22. The method according to any one of claims 1 to 21, wherein, The weight-volume concentration of the active ingredient is selected to be from 0.1% to 0.4%, for example, from 0.04% to 0.08%.

23. The method according to any one of claims 1 to 20, wherein, The weight-volume concentration of the active ingredient is selected as approximately 0.007%, approximately 0.0087%, approximately 0.009%, approximately 0.01%, approximately 0.02%, approximately 0.03%, approximately 0.04%, approximately 0.05%, approximately 0.06%, approximately 0.07%, approximately 0.08%, approximately 0.09%, approximately 0.2%, approximately 0.3%, approximately 0.7%, and approximately 1%.

24. The method according to any one of claims 1 to 23, wherein, The mixture further comprises other pharmaceutical excipients selected from one or more of the following: antibacterial agents, pH adjusters, and osmotic pressure adjusters; Optionally, the antibacterial agent is selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol; Optionally, the pH adjuster is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane. Optionally, the osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol.

25. The method according to claim 24, wherein, The weight-volume concentration of the antibacterial agent is not greater than 0.05%, for example not greater than 0.02%, or even more specifically not greater than 0.01%.

26. The method according to claim 24 or 25, wherein, The antibacterial agent has a weight-volume concentration of 0.01% to 0.02%, for example, 0.01% to 0.015%.

27. The method according to claim 24, wherein, The antibacterial agent has a weight-volume concentration of 0.005% to 0.02%, for example, 0.005% to 0.015%.

28. The method according to claim 24, wherein, The weight-volume concentration of the antibacterial agent is selected from one of about 0.002%, about 0.003%, about 0.005%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.0125%, about 0.015%, and about 0.02%.

29. The method according to any one of claims 1 to 28, wherein, The mixture has a pH of 7 or lower.

30. The method according to any one of claims 1 to 29, wherein, The pH of the mixture is between 5 and 7.

31. The method according to any one of claims 1 to 30, wherein, The pH of the mixture is between 5.5 and 7.

32. The method according to any one of claims 1 to 31, wherein, The pH of the mixture is between 5.5 and 6.

5.

33. The method according to any one of claims 1 to 32, wherein, The osmotic pressure of the mixture is 330 to 350 mOsm / kg.

34. The method according to any one of claims 1 to 33, wherein, The mixture is prepared as a nasal spray or nasal drops.

35. Use of glucose polymers or derivatives thereof in the preparation of an absorption enhancer as defined in any one of claims 1 to 34.

36. Use of glucose polymers or derivatives thereof as absorption enhancers in the preparation of mixtures as defined in any one of claims 1 to 35.

37. The method according to any one of claims 1 to 36, wherein, The mixture contains brain tissue T cells for less than 10 minutes. max .

38. The method according to any one of claims 1 to 37, wherein, The mixture contains brain tissue T cells for less than 5 minutes. max .

39. The method according to any one of claims 1 to 38, wherein, The mixture contains brain tissue T cells for no more than 15 minutes. max .

40. The method according to any one of claims 1 to 39, wherein, AUC of brain tissue providing the active ingredient in the absence of the absorption enhancer 0-t In comparison, the mixture provides more of the corresponding brain tissue AUC. 0-t .

41. The method according to any one of claims 1 to 40, wherein, AUC of brain tissue providing the active ingredient in the absence of the absorption enhancer 0-t In comparison, the mixture provides 1.1 times or more of the corresponding brain tissue AUC. 0-t .

42. The method according to any one of claims 1 to 41, wherein, AUC of brain tissue providing the active ingredient in the absence of the absorption enhancer 0-t In comparison, the mixture provides 1.5 times or more of the corresponding brain tissue AUC. 0-t .

43. The method according to any one of claims 1 to 42, wherein, AUC of brain tissue providing the active ingredient in the absence of the absorption enhancer 0-t In comparison, the mixture provides 3 times or more of the corresponding brain tissue AUC. 0-t .

44. The method according to any one of claims 1 to 43, wherein, Compared with brain tissue C in the absence of the absorption enhancer, which provides the active ingredient max In comparison, the mixture provides more of the corresponding brain tissue C. max For example, not less than 1.1 times, or not less than 1.3 times.

45. The method according to any one of claims 1 to 44, wherein, C provides the active ingredient in the absence of the absorption enhancer. max-脑组织 / C max-血浆 In comparison, the mixture provides 1.1 times or more of the corresponding C max-脑组织 / C max-血浆 For example, not less than 1.2 times, not less than 1.3 times, not less than 1.4 times, not less than 1.5 times, or not less than 2 times.

46. ​​The method according to any one of claims 1 to 45, wherein, AUC of the active ingredient provided in the absence of the absorption enhancer 0-t-脑组织 / AUC 0-t-血浆 In comparison, the mixture provides 1.1 times or more of the corresponding AUC. 0-t-脑组织 / AUC 0-t-血浆 For example, not less than 1.3 times.

47. Use of a glucose polymer or its derivative as an absorption enhancer in the preparation of nasal compositions, compositions delivered via cranial nerves, intracranial and / or central nervous system, or compositions delivered via cranial nerves to the intracranial and / or central nervous system, wherein optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V, or optionally, the absorption enhancer does not contain any other absorption enhancers besides the glucose polymer or its derivative; optionally, the composition contains an active ingredient.

48. Use of a glucose polymer or a derivative thereof in the preparation of an absorption enhancer for use as an active ingredient administered nasally, for delivery of an active ingredient to cranial nerves, the brain and / or the central nervous system, or for delivery of an active ingredient to the brain and / or the central nervous system via cranial nerves, wherein optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V, or optionally, the absorption enhancer does not contain any other absorption enhancers besides the glucose polymer or a derivative thereof; optionally, the absorption enhancer is contacted with the active ingredient to form a composition.

49. The use according to claim 47 or 48, wherein the combination further comprises a pharmaceutical excipient, optionally, the pharmaceutical excipient being selected from one or more of: antibacterial agents, pH adjusters, and osmotic pressure adjusters; Optionally, the antibacterial agent is selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol; Optionally, the pH adjuster is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane. Optionally, the osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol.

50. Use of antibacterial agents or antibacterial synergists containing glucose polymers or their derivatives in the preparation of compositions containing active ingredients.

51. The use according to claim 50, wherein, The antibacterial agent or antibacterial synergist does not contain any other antibacterial agent or antibacterial synergist besides the glucose polymer or its derivatives.

52. In the use according to claim 50 or 51, when the glucose polymer or its derivative is used as an antibacterial synergist, the composition contains an antibacterial agent selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol.

53. The use according to any one of claims 50 to 52, wherein when the glucose polymer or its derivative is used as an antibacterial agent or an antibacterial synergist, the combination further comprises other pharmaceutical excipients, optionally, the pharmaceutical excipients being selected from one or more of pH adjusters and / or osmotic pressure adjusters; Optionally, the pH adjuster is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane. Optionally, the osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol.

54. The use according to any one of claims 47 to 53, wherein, The glucose polymer or its derivatives are selected from one or more of the following: dextran, α-glucan, oat β-glucan, fungal β-glucan, yeast β-glucan, seaweed β-glucan, icodextrin, polydextrose, starch, or derivatives of any of the foregoing.

55. The use according to claim 54, wherein, The dextran is selected from one or more of dextran 10, dextran 20, dextran 40, dextran 60, dextran 70, and macromolecular dextran.

56. The use according to claim 54, wherein the dextran is selected from dextran 5.

57. The use according to any one of claims 54 to 56, wherein, The dextran or its derivative has a weight-volume concentration of at least 1%, for example at least 2%, for example at least 5%.

58. The use according to any one of claims 54 to 57, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 20%.

59. The use according to any one of claims 54 to 58, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 10%.

60. The use according to any one of claims 54 to 59, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 5%.

61. The use according to any one of claims 54 to 56, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 20%.

62. The use according to any one of claims 54 to 56, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 10%.

63. The use according to any one of claims 54 to 56, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 5%.

64. The use according to any one of claims 54 to 56, wherein, The weight-volume concentration of the dextran or its derivative is selected from one of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, and about 13%.

65. The use according to any one of claims 54 to 56, wherein, The weight-volume concentration of the dextran or its derivative is selected from 0.1% to 0.4%, 0.4% to 2%, 0.4% to 10%, and / or 0.1% to 20%.

66. The use according to any one of claims 47 to 65, wherein, The active ingredient is selected from one or more of the following: sumatriptan, zolmitriptan, dexmedetomidine, nalmefen, zavigepan, naloxone, diazepam, cocaine, midazolam, estaketone, dihydroergotamine, budesonide, fluticasone, bromocriptine, doxepin, fentanyl, propofol, nitrazepam, estazolam, oxazepam, zolpidem, triazolam, diazepam, nitrazepam. Fluazinam, clonazepam, buspirone, fluvoxamine, paroxetine, trazodone, mirtazapine, chlorpromazine, clozapine, mirtazapine, olanzapine, promethazine, zaleplon, alprazolam, eszopiclone, amitriptyline, doxepin, sertraline, lorazepam, clonazepam, duspironone, zopiclone, propranolol, citalopram, escitalopram, duloxetine, venlafaxine, Tramadol, morphine, meperidine, codeine, sufentanil, carbamazepine, sodium valproate, phenobarbital, lamotrigine, levetiracetam, oxcarbazepine, phenytoin sodium, primidone, gabapentin, tocopherol, vigabatrin, fluoxetine, mirtamine, donepezil, rivastigmine, galantamine, memantine, amantadine, levodopa, rotigotine, rasagiline, pramipexole, ropinirole, piribedil, rotigotine, trihexyphenidyl, tocapone, entacapone, buphenazine, atomoxetine, methylphenidate, amphetamine, quetiapine, perphenazine, sulpiride, aripiprazole, amisulpride, ziprasidone, buspirone, haloperidol, lurasidone, paliperidone, modafinil, telolide, any pharmaceutically acceptable salt, solvate, or isomer of any of the foregoing drugs.

67. The use according to any one of claims 47 to 65, wherein, The active ingredient is selected from 7,8-dihydroxyflavone and its pharmaceutically acceptable salts, solvates or isomers thereof.

68. The use according to claim 66 or 67, wherein, The pharmaceutically acceptable salt is selected from one or more of the following: propionate, hydrochloride, sulfate, nitrate, hydrobromide, hydroiodide, tartrate, formate, citrate, acetate, trichloroacetate, trifluoroacetate, gluconate, benzoate, lactate, fumarate, maleate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, and naphthalenesulfonate.

69. The use according to any one of claims 47 to 66, wherein, The active ingredient is dexmedetomidine or its hydrochloride salt.

70. The use according to any one of claims 47 to 66, wherein the glucose polymer or a derivative thereof is dextran 70.

71. The use according to any one of claims 49 to 70, wherein, The weight-volume concentration of the antibacterial agent is not greater than 0.05%, for example, not greater than 0.02%, for example, not greater than 0.01%.

72. The use according to any one of claims 49 to 70, wherein, The antibacterial agent has a weight-volume concentration of 0.01% to 0.02%, for example, 0.01% to 0.015%.

73. The use according to any one of claims 49 to 70, wherein, The antibacterial agent has a weight-volume concentration of 0.005% to 0.02%, for example, 0.005% to 0.015% or 0.005% to 0.01%.

74. The use according to any one of claims 49 to 70, wherein, The weight-volume concentration of the antibacterial agent is selected from one of about 0.002%, about 0.003%, about 0.005%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.0125%, about 0.015%, and about 0.02%.

75. The use according to any one of claims 47 to 74, wherein, The composition has a pH of 7 or less.

76. The use according to any one of claims 47 to 75, wherein, The pH value of the composition is 5 to 7.

77. The use according to any one of claims 47 to 76, wherein, The pH value of the composition is 5.5 to 7.

78. The use according to any one of claims 47 to 77, wherein, The pH value of the composition is 5.5 to 6.

5.

79. The use according to any one of claims 47 to 78, wherein, The composition has an osmotic pressure of 330 to 350 mOsm / kg.

80. The use according to any one of claims 47 to 79, wherein, The active ingredient is a therapeutically effective amount of dexmedetomidine, for example, the weight-volume concentration of dexmedetomidine is selected to be 0.004% to 1.2%.

81. The use according to any one of claims 47 to 80, wherein, The weight-volume concentration of the active ingredient is selected to be between 0.02% and 0.12%.

82. The use according to any one of claims 47 to 81, wherein, The weight-volume concentration of the active ingredient is selected to be from 0.1% to 0.4%, for example, from 0.04% to 0.08%.

83. The use according to any one of claims 47 to 80, wherein, The weight-volume concentration of the active ingredient is selected as approximately 0.007%, approximately 0.0087%, approximately 0.009%, approximately 0.01%, approximately 0.02%, approximately 0.03%, approximately 0.04%, approximately 0.05%, approximately 0.06%, approximately 0.07%, approximately 0.08%, approximately 0.09%, approximately 0.2%, approximately 0.3%, approximately 0.7%, and approximately 1%.

84. A use according to any one of claims 47 to 83, wherein, The composition is prepared as a nasal spray or nasal drops.

85. A composition for delivering an active ingredient via nasal route or to cranial nerves, the brain, and / or the central nervous system, comprising: (a) Active ingredients; and (b) Glucose polymers or their derivatives; The glucose polymer or its derivatives serve as absorption promoters and / or antibacterial agents or antibacterial synergists. Optionally, the cranial nerve is selected from one or both of cranial nerve I and cranial nerve V.

86. The composition according to claim 85, wherein, The composition does not contain any absorption enhancers or antibacterial synergists other than the glucose polymer or its derivatives.

87. The composition according to claim 85, wherein, The composition does not contain any antibacterial agents other than the glucose polymer or its derivatives.

88. The composition according to any one of claims 85 to 87, wherein, The active ingredient is selected from one or more of the following: sumatriptan, zolmitriptan, dexmedetomidine, nalmefen, zavigepan, naloxone, diazepam, cocaine, midazolam, estaketone, dihydroergotamine, budesonide, fluticasone, bromocriptine, doxepin, fentanyl, propofol, nitrazepam, estazolam, oxazepam, zolpidem, triazolam, diazepam, nitrazepam. Fluazinam, clonazepam, buspirone, fluvoxamine, paroxetine, trazodone, mirtazapine, chlorpromazine, clozapine, mirtazapine, olanzapine, promethazine, zaleplon, alprazolam, eszopiclone, amitriptyline, doxepin, sertraline, lorazepam, clonazepam, duspironone, zopiclone, propranolol, citalopram, escitalopram, duloxetine, venlafaxine, Tramadol, morphine, meperidine, codeine, sufentanil, carbamazepine, sodium valproate, phenobarbital, lamotrigine, levetiracetam, oxcarbazepine, phenytoin sodium, primidone, gabapentin, tocopherol, vigabatrin, fluoxetine, mirtamine, donepezil, rivastigmine, galantamine, memantine, amantadine, levodopa, rotigotine, rasagiline, pramipexole, ropinirole, piribedil, rotigotine, trihexyphenidyl, tocapone, entacapone, buphenazine, atomoxetine, methylphenidate, amphetamine, quetiapine, perphenazine, sulpiride, aripiprazole, amisulpride, ziprasidone, buspirone, haloperidol, lurasidone, paliperidone, modafinil, telolide, any pharmaceutically acceptable salt, solvate, or isomer of any of the foregoing drugs.

89. The composition according to claim 85, wherein, The active ingredient is selected from 7,8-dihydroxyflavone and its pharmaceutically acceptable salts, solvates or isomers thereof.

90. The composition according to claim 88 or 89, wherein, The pharmaceutically acceptable salt is selected from one or more of the following: propionate, hydrochloride, sulfate, nitrate, hydrobromide, hydroiodide, tartrate, formate, citrate, acetate, trichloroacetate, trifluoroacetate, gluconate, benzoate, lactate, fumarate, maleate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, and naphthalenesulfonate.

91. The composition according to any one of claims 85 to 90, wherein, The glucose polymer or its derivatives are selected from one or more of the following: dextran, α-glucan, oat β-glucan, fungal β-glucan, yeast β-glucan, seaweed β-glucan, icodextrin, polydextrose, starch, or derivatives of any of the foregoing.

92. The composition according to claim 91, wherein, The dextran is selected from one or more of dextran 10, dextran 20, dextran 40, dextran 60, dextran 70 and macromolecular dextran.

93. The composition according to claim 91, wherein the dextran is selected from dextran 5.

94. The composition according to any one of claims 91 to 93, wherein, The weight-volume concentration of the dextran or its derivative is at least 1%, for example at least 2%, and even more specifically at least 5%.

95. The composition according to any one of claims 91 to 93, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 20%.

96. The composition according to any one of claims 91 to 93, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 10%.

97. The composition according to any one of claims 91 to 93, wherein, The dextran or its derivative has a weight-volume concentration of 1% to 5%.

98. The composition according to any one of claims 91 to 93, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 20%.

99. The composition according to any one of claims 91 to 93, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 10%.

100. The composition according to any one of claims 91 to 93, wherein, The dextran or its derivative has a weight-volume concentration of 2% to 5%.

101. The composition according to any one of claims 91 to 93, wherein, The weight-volume concentration of the dextran or its derivative is selected from one of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, and about 13%.

102. The composition according to any one of claims 91 to 93, wherein, The weight-volume concentration of the dextran or its derivative is selected from 0.1% to 0.4%, 0.4% to 2%, 0.4% to 10%, and / or 0.1% to 20%.

103. The composition according to any one of claims 85 to 88 and claims 90 to 102, wherein, The active ingredient is dexmedetomidine or its hydrochloride salt.

104. The composition according to any one of claims 85 to 92 and claims 94 to 103, wherein, The glucose polymer is dextran 70.

105. The composition according to any one of claims 85 to 88 and claims 90 to 104, wherein, The active ingredient is a therapeutically effective amount of dexmedetomidine, for example, the weight-volume concentration of dexmedetomidine is selected to be 0.004% to 1.2%.

106. The composition according to any one of claims 85 to 105, wherein, The weight-volume concentration of the active ingredient is selected to be between 0.02% and 0.12%.

107. The composition according to any one of claims 85 to 106, wherein, The weight-volume concentration of the active ingredient is selected to be from 0.1% to 0.4%, for example, from 0.04% to 0.08%.

108. The composition according to any one of claims 85 to 105, wherein, The weight-volume concentration of the active ingredient is selected as approximately 0.007%, approximately 0.0087%, approximately 0.009%, approximately 0.01%, approximately 0.02%, approximately 0.03%, approximately 0.04%, approximately 0.05%, approximately 0.06%, approximately 0.07%, approximately 0.08%, approximately 0.09%, approximately 0.2%, approximately 0.3%, approximately 0.7%, and approximately 1%.

109. The composition according to any one of claims 85 to 108, wherein, It further includes other pharmaceutical excipients, optionally selected from one or more of the following: antibacterial agents, pH adjusters, and osmotic pressure adjusters; Optionally, the antibacterial agent is selected from one or more of benzalkonium chloride, benzalkonium bromide, quaternary ammonium salts, cetrimonium bromide, phenoxyethanol, sodium benzoate, and phenethyl alcohol; Optionally, the pH adjuster is selected from one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, diethanolamine, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and tris(hydroxymethyl)aminomethane. Optionally, the osmotic pressure regulator is selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerol, and propylene glycol.

110. The composition according to claim 109, wherein, The weight-volume concentration of the antibacterial agent is not greater than 0.05%, for example not greater than 0.02%, or even more specifically not greater than 0.01%.

111. The composition according to claim 109, wherein, The antibacterial agent has a weight-volume concentration of 0.01% to 0.02%, for example, 0.01% to 0.015%.

112. The composition according to claim 109, wherein, The antibacterial agent has a weight-volume concentration of 0.005% to 0.02%, for example, 0.005% to 0.015%.

113. The composition according to claim 109, wherein, The weight-volume concentration of the antibacterial agent is selected from one of about 0.002%, about 0.003%, about 0.005%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.0125%, about 0.015%, and about 0.02%.

114. The composition according to any one of claims 85 to 113, wherein, The composition has a pH of 7 or less.

115. The composition according to any one of claims 85 to 114, wherein, The pH value of the composition is 5 to 7.

116. The composition according to any one of claims 85 to 115, wherein, The pH value of the composition is 5.5 to 7.

117. The composition according to any one of claims 85 to 116, wherein, The pH value of the composition is 5.5 to 6.

5.

118. The composition according to any one of claims 85 to 117, wherein, The composition has an osmotic pressure of 330 to 350 mOsm / kg.

119. The composition according to any one of claims 85 to 118, wherein, The composition is prepared as a nasal spray or nasal drops.

120. A formulation comprising the composition according to any one of claims 85 to 118, wherein, The formulation is selected from nasal sprays or nasal drops.

121. The composition according to any one of claims 85 to 120, and its use in the preparation of a sedative, hypnotic, anxiolytic, stress-reducing, anesthetic, analgesic, arousal-promoting, antidepressant, antiepileptic, anti-agitation, anti-excitement, treatment of insomnia, treatment of schizophrenia, treatment of acute transient psychotic disorder, treatment of schizoaffective disorder, treatment of schizotypal disorder, treatment of delusional disorder, treatment of depressive disorder, treatment of anxiety disorder, treatment of bipolar disorder, treatment of obsessive-compulsive disorder and related disorders, treatment of dissociative disorder, treatment of somatic discomfort or somatic experience disorder, treatment of Parkinson's disease, treatment of attention deficit hyperactivity disorder, treatment of tic disorder, treatment of mania, treatment of autism spectrum disorder, treatment of oppositional defiant disorder, treatment of intermittent rage disorder, treatment of substance use disorder, treatment of delirium, treatment of post-traumatic stress disorder, treatment of acute stress disorder, and treatment of adjustment disorder.

122. A method of treating a disease, comprising administering to a subject the composition of any one of claims 85 to 120, wherein the disease is selected from sedation, hypnosis, anxiety, stress response, anesthesia, analgesia, arousal, depression, epilepsy, agitation, agitation, insomnia, schizophrenia, treatment of acute transient psychotic disorder, treatment of schizoaffective disorder, treatment of schizotypal disorder, treatment of delusional disorder, treatment of depressive disorder, treatment of anxiety disorder, treatment of bipolar disorder, treatment of obsessive-compulsive disorder and related disorders, treatment of dissociative disorder, treatment of somatic discomfort or somatic experience disorder, treatment of Parkinson's disease, treatment of attention deficit hyperactivity disorder, treatment of tic disorder, treatment of mania, treatment of autism spectrum disorder, treatment of oppositional defiant disorder, treatment of intermittent rage disorder, treatment of substance use disorder, treatment of delirium, post-traumatic stress disorder, treatment of acute stress disorder, and treatment of adjustment disorder.

123. The composition according to any one of claims 85 to 120, for use as a sedative, hypnotic, anti-anxiety, stress-reducing, anesthetic, analgesic, arousal-promoting, antidepressant, anti-epileptic, anti-agitation, agitation-inhibiting, treatment of insomnia, treatment of schizophrenia, treatment of acute transient psychotic disorder, treatment of schizoaffective disorder, treatment of schizotypal disorder, treatment of delusional disorder, treatment of depressive disorder, treatment of anxiety disorder, treatment of bipolar disorder, treatment of obsessive-compulsive disorder and related disorders, treatment of dissociative disorder, treatment of somatic discomfort or somatic experience disorder, treatment of Parkinson's disease, treatment of attention deficit hyperactivity disorder, treatment of tic disorder, treatment of mania, treatment of autism spectrum disorder, treatment of oppositional defiant disorder, treatment of intermittent rage disorder, treatment of substance use disorder, treatment of delirium, treatment of post-traumatic stress disorder, treatment of acute stress disorder, and treatment of adjustment disorder.

124. A method for preparing the composition of any one of claims 85 to 123, comprising, This allows the various components in the composition to come into contact.

125. A device for intranasal drug delivery, wherein, The device contains the composition according to any one of claims 85 to 124.

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