CN-121971456-A - Pharmaceutical composition for treating hormone-resistant severe asthma and application thereof

Abstract

The invention belongs to the technical field of medicinal chemistry, and in particular relates to a medicinal composition for treating hormone-resistant severe asthma and application thereof. Use of Pentagalloylglucose (PGG) in the manufacture of a medicament for the treatment or prevention of hormone refractory type severe asthma. Especially, the traditional Chinese medicine composition has better effect on the symptoms of emphysema caused by severe asthma. The present invention reveals and demonstrates for the first time that intestinal damage is a key upstream factor leading to severe asthma and hormonal resistance. Through targeted repair of intestinal tracts, PGG can radically remodel the immune microenvironment of the lung, thereby creating conditions for hormone to play a role. The discovery breaks through the limitation that the traditional asthma treatment is only focused on local targets of respiratory tracts, and provides a brand-new theoretical basis and a feasible solution for overcoming the worldwide difficult problem of hormone resistance.

Inventors

• CAO GANG
• SANG XIANAN

Assignees

• 浙江中医药大学

Dates

Publication Date

20260505

Application Date

20251231

Claims (10)

1. 1. Use of pentagalloylglucose in the manufacture of a medicament for the treatment or prevention of hormone-resistant severe asthma.
2. 2. The use according to claim 1, comprising the use of the medicament in combination with a glucocorticoid to overcome or reduce the resistance of the severe asthmatic patient to the glucocorticoid.
3. 3. The use according to claim 1 or 2, wherein the medicament exerts a therapeutic or prophylactic effect by modulating the intestinal-pulmonary axis of the patient.
4. 4. The use according to claim 1, wherein the hormone-resistant severe asthma is non-Th 2 type severe asthma or neutrophilic severe asthma.
5. 5. A pharmaceutical composition or combination kit comprising a therapeutically effective amount of pentagalloylglucose and a glucocorticoid, and pharmaceutically acceptable excipients.
6. 6. A pharmaceutical composition characterized in that the active ingredients thereof consist of 8-O-debenzoyl paeoniflorin and pentagalloylglucose, optionally further comprising paeoniflorin and/or white peony root crude polysaccharide.
7. 7. The pharmaceutical composition according to claim 6, wherein the active ingredient consists of 8-O-debenzoyl paeoniflorin and pentagalloyl glucose, or the active ingredient consists of 8-O-debenzoyl paeoniflorin, pentagalloyl glucose and paeoniflorin.
8. 8. Use of a pharmaceutical composition according to claim 6 for the manufacture of a medicament for the treatment or prophylaxis of severe asthma.
9. 9. The use according to claim 8, wherein the severe asthma is hormone-resistant severe asthma or inflammatory severe asthma.
10. 10. The use according to claim 8, comprising the use of the pharmaceutical composition in combination with a glucocorticoid to produce a synergistic therapeutic effect.

Description

Pharmaceutical composition for treating hormone-resistant severe asthma and application thereof Technical Field The invention belongs to the technical field of medicinal chemistry, and in particular relates to a medicinal composition for treating hormone-resistant severe asthma and application thereof. Background Respiratory diseases have long been seen as a serious public health challenge worldwide, with severe respiratory diseases being more heavily burdened by high morbidity, high disability and mortality, in patients, families and society. The severe asthma has complex condition and rapid change, is easy to induce acute respiratory failure, causes circulatory failure and sudden cardiac arrest, and is a serious life-threatening internal medicine emergency. Severe asthma refers to patients who, after exclusion of patient compliance and drug inhalation technology factors, are not able to achieve effective control even after regular combination of high-dose glucocorticoid inhalants with long-acting beta 2 receptor agonists for 3 months or more, and adequately manage controllable factors, or who are again out of control of asthma symptoms after degradation treatment. Severe asthma is a key factor in disabling and fatal conditions in asthmatics, and is 5-fold more risky than mild to moderate asthma. Severe asthma (SEVERE ASTHMA), while accounting for only 5% -10% of asthmatics, consumes over 50% of the medical resources and its treatment presents serious challenges. The clinic is currently mainly dependent on large doses of inhaled glucocorticoids (ICS) in combination with long acting beta 2 receptor agonists (LABA), but about 30% -50% of patients show hormonal resistance and even increased doses still have difficulty in controlling symptoms. In recent years, targeted biological agents (e.g., anti-IgE, anti-IL-5/IL-5R mAbs) hold promise for a subset of patients, but high treatment costs (tens of thousands of dollars in annual) and stringent phenotypic screening have limited their widespread use. Of particular concern, about 40% of severe asthma is of the non-Th 2 type (e.g., neutrophilic type) for which existing biological agents are nearly ineffective. There is a great clinical need to develop new therapeutic strategies that can modulate systemic immune homeostasis, reduce hormone dependence, and be suitable for a broad spectrum of asthma phenotypes. However, current exploration of the pathogenesis of severe asthma remains limited, especially the understanding of its association with systemic inflammation and dysfunction of distant organs (e.g., the intestinal tract) is unclear, which greatly limits the development of innovative therapies. Disclosure of Invention The invention aims to overcome the defects of the prior art and provide a medicament for treating hormone-resistant severe asthma. The present inventors have conducted intensive studies and, for the first time, have surprisingly found that the occurrence and development of severe asthma, in particular, the occurrence of hormone resistance phenomenon, is closely related to intestinal damage and the resultant "intestinal-pulmonary axis" dysfunction. In particular, intestinal lesions result in the loss of the pulmonary innate immune cells ILC2s, forming "immune voids" that cause the lungs to develop abnormal and hormone-insensitive inflammatory responses when stimulated by the outside world. Based on this significant finding, the present invention creatively proposes a new paradigm of "enterally treating the lung" treatment and is achieved by: in a first aspect, the inventors have demonstrated for the first time that the known compound Pentagalloylglucose (PGG) is capable of restoring the immune homeostasis of the "gut-lung axis" by specifically repairing intestinal lesions ("modulating the intestines"), thus effectively overcoming the hormonal resistance of severe asthma and producing a synergistic therapeutic effect with glucocorticoids. In a second aspect, based on the above findings, the present inventors have further developed a novel compound pharmaceutical composition comprising not only the core active ingredient PGG, but also being scientifically compatible with other natural products having potential synergistic effects, which, when combined with glucocorticoids, exhibits a far-unexpected, powerful synergistic effect, can almost completely inhibit airway remodeling, hinder the development of lung qi and restore impaired lung function. In order to achieve the above purpose, the present invention specifically provides the following technical solutions: Scheme one novel use of Pentagalloylglucose (PGG) Use of Pentagalloylglucose (PGG) in the manufacture of a medicament for the treatment or prevention of hormone refractory type severe asthma. Especially, the traditional Chinese medicine composition has better effect on the symptoms of emphysema caused by severe asthma. Preferably, the use comprises the use of the medicament in combination with a