CN-122005511-A - Atomized composition and application thereof

Abstract

The invention relates to the technical field of pharmaceutical compositions, in particular to an atomization composition and application thereof. The aerosolized composition comprises A) an MSC-derived active ingredient selected from any one or combination of (i) MSC exosomes/extracellular vesicles, (ii) MSC conditioned medium concentrate, (iii) MSC lysate, (iv) MSC-derived soluble factors, (v) immobilized/entrapped protected MSC or fragments thereof, (B) Ergothioneine (EGT) or a pharmaceutically acceptable salt thereof, and C) a pharmaceutically acceptable carrier/buffer system, making it suitable for aerosol inhalation administration. The combination of exosomes and ergothioneine remarkably improves the effectiveness of sleep improvement through the cooperation of nerve regulation and cytoprotection mechanisms, and the introduction of an atomization administration technology breaks through the limitation of the traditional therapy from the multi-dimension aspects of non-invasive, precise delivery, personalized treatment, accessibility and the like, so that wider crowds (including special crowds) can safely and conveniently receive high-efficiency treatment.

Inventors

• Yang mingjia
• WANG PENG
• LI RONG
• FAN HONGLIU
• YANG XIANLAN
• LI CHUAN
• YANG YUANYUAN
• LIU JIA
• FAN LING
• ZHU XINTING

Assignees

• 四川天府亨特生命科技有限公司

Dates

Publication Date

20260512

Application Date

20260416

Claims (6)

1. 1. An atomized composition of matter which comprises a base material, characterized by comprising: a) An MSC-derived active ingredient selected from any one or a combination of the following: (i) MSC exosomes/extracellular vesicles, (Ii) MSC-conditioned medium concentrate, and, (Iii) The lysate of the MSCs was used to prepare the cells, (Iv) The MSCs are derived from the soluble factors, (V) Immobilized/embedded protected MSCs or fragments thereof; B) Ergothioneine or a pharmaceutically acceptable salt thereof, and C) A pharmaceutically acceptable carrier/buffer system, which is suitable for administration by aerosol inhalation, wherein the pharmaceutically acceptable carrier is trehalose, human serum albumin and poloxamer.
2. 2. The atomizing composition according to claim 1, wherein the atomizing composition contains 0.1 to 1% by mass of ergothioneine per ml of the solution containing 100 to 1000 million exosome particles.
3. 3. The aerosolized composition of claim 1, wherein the buffer system is selected from one or more of the group consisting of physiological saline, ringer's solution, a colloidal solution, a human albumin solution, a phosphate buffer solution, and a carbonate buffer solution.
4. 4. The aerosolized composition of claim 1, wherein the pharmaceutically acceptable salt of ergothioneine comprises ergothioneine hydrochloride, ergothioneine sulfate, or ergothioneine hydrobromide.
5. 5. Use of a nebulized composition according to any one of claims 1 to 4 for the preparation of a medicament for improving sleep.
6. 6. The use according to claim 5, wherein sleep improvement is one or more selected from the group consisting of shortening the latency to sleep, reducing the time and number of mid-wake events, and increasing the ratio of non-fast eye movement sleep time to overall sleep time.

Description

Atomized composition and application thereof Technical Field The invention relates to the technical field of pharmaceutical compositions, in particular to an atomization composition and application thereof. Background Insomnia and various sleep disorders have constituted a significant public health challenge worldwide. Epidemiological data shows that hundreds of millions of people are profoundly disturbed worldwide, with prevalence of chronic insomnia remaining high. In China, the problem is also increasingly remarkable, and the quality of life and the working efficiency of people are obviously impaired. Sleep disorders are complex and diverse in appearance, including difficulty falling asleep, shallow wakefulness, early wakefulness, lack of sleep, etc., often accompanied by daytime fatigue, inattention, and emotional problems. More seriously, the long-term sleep disorder is an important risk factor of various chronic diseases such as cardiovascular and cerebrovascular diseases, metabolic abnormality, depression anxiety, cognitive decline and the like. Therefore, development of sleep improvement schemes which are good in effect, high in safety and convenient to obtain has urgent clinical and social demands. The current mainstream of drug treatment depends on benzodiazepines and non-benzodiazepine sedative hypnotic drugs. Although the medicine can induce sleep quickly, the long-term application has obvious limitation, such as addiction and dependence risk, possibly causing cognitive side effects such as memory damage, slow response and the like, and increasing the falling risk of the old. In addition, the development of drug tolerance often results in the need for ever increasing doses, and interactions with other centrally inhibiting drugs also present a safety hazard. On the other hand, although non-drug intervention such as cognitive behavior therapy has no drug side effect, professional guidance and longer treatment period are needed, patient compliance is different, and urgent requirements of acute or severe insomnia patients on quick and remarkable curative effects are difficult to meet. Overall, existing therapies focus on temporarily suppressing arousal or altering behavioral cognition, and lack fundamental repair and modulation means for intrinsic impairment and dysfunction of the sleep-modulating neural circuits. In recent years, ergothioneine has been found to have sleep improving effects. Ergothioneine can participate in redox reactions as an antioxidant molecule, reducing linkage damage (especially membrane lipid peroxidation) caused by excessive ROS. This is critical for sleep regulation, as lipid peroxidation of nerve cell membranes can interfere with ion channel function, receptor activity and synaptic transmission efficiency, resulting in increased background "noise" of the neural network, decreased arousal threshold, and thus, difficulty in sleep maintenance and fragmentation. By protecting cell membrane structures, ergothioneine helps stabilize neuroelectrical activity, potentially enhancing sleep continuity. In addition, it can protect mitochondria, maintain energy metabolism steady state of neuron, avoid nerve excitability abnormality caused by "energy crisis", and indirectly inhibit nerve inflammation related to it by relieving oxidative stress. At the neurochemical level, ergothioneine has regulatory potential on neurotransmitter systems closely related to the sleep-wake cycle, such as dopamine, serotonin, GABA, etc., possibly helping to restore the intrinsic balance of the nervous system. However, despite the considerable promise, ergothioneine has low bioavailability, and it is difficult to achieve effective therapeutic concentrations in vivo, such that its theoretical beneficial effects of neuroprotection, antioxidant and transmitter modulation are not fully realized. This may be one of the important reasons that the individual supplementation of ergothioneine sometimes only improves subjective fatigue sensation and does not significantly improve objective sleep indexes (such as latency to sleep, number of night wakefulness, etc.), namely, the occurrence of a disjoint phenomenon that "body sensation is improved but sleep structure is not fundamentally optimized" in clinical observation. Thus, existing intervention strategies have gaps between safety and radical cure. The development of a novel therapeutic scheme which can avoid the risks of traditional medicines and break through the delivery limit of medicines so as to accurately exert the functions of neuroprotection and steady-state regulation and radically improve the sleep quality becomes a very valuable research and development direction which is yet to be filled. Furthermore, since the inventors herein have studied numerous documents and patents, on the one hand, and have not set forth in detail all the details and content of the invention for the purpose of understanding the differences to those skilled in the art, on the ot