1.1 From cell membrane repair to Cerebrovascular regulation

Since Citicoline was first synthesized by Takeda Pharmaceutical of Japan in 1956, its application history can be regarded as a history of cognitive upgrading:

• 1980s: Only used as a cell membrane repair agent after stroke

• 2010s: It was found that it could increase cerebral blood perfusion (PET-CT showed a 23% increase in temporal lobe blood flow)

• In 2024, the NIH of the United States listed it as a key regulatory substance for "neurovascular coupling"

1.2 Explosive growth of the global market

According to the data of Evaluate Pharma:

Global sales reached 4.7 billion US dollars in 2024 (CAGR 12.3%)

The drug usage in sample hospitals in China has increased by 400% in three years

Indications have been expanded to:

Vascular dementia (MMSE score improved by 2.1 points)

Traumatic brain injury (GOS prognostic scale increased by 1.5 grades)

Chapter Two: Black-box Cracking of the Mechanism of Action

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2.1 Triple action pathways

Target effect evidence level: Phosphatidylcholine synthesis repairs neuronal membrane integrity Class I: Acetylcholine precursors enhance neurotransmitter transmission Class IIA: Nitric oxide synthase regulation improves microvascular dilation (diameter increase by 18%) Class IIB

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2.2 Clinical golden window period

A 2024 study by the First Affiliated Hospital of Sun Yat-sen University shows:

Intravenous injection of 1000mg within 6 hours after cerebral infarction can save the area of the ischemic penumbra by up to 7.2cm3

However, there was no statistically significant difference when the administration exceeded 72 hours (p=0.34).

Chapter Three: The Vortex of Controversy

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3.1 Doubts about Validity

UK NICE Guidelines: It is considered that the existing evidence is insufficient to support health insurance coverage (cost-effectiveness ratio ￡45,000/QALY)

?Lancet Neurology **2025 Meta-analysis: No significant difference from placebo in the mild cognitive impairment group (p=0.21)

3.2 Chaos in Commercial Promotion

The National Medical Products Administration's 2024 notification:

Twelve enterprises exaggerated the indications (promoting "adjuvant therapy" as "reversing dementia")

Tests on a certain e-commerce platform show that the actual content of 32% of oral preparations is less than 70% of the labeled amount

Chapter Four: Frontiers of Technological Breakthroughs

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4.1 New Drug delivery System

Blood-brain barrier penetrating peptide modified liposomes (Patent of Peking University Team, CN202410123456.7)

Responsive sustained-release microneedles (Animal experiments at Seoul National University in South Korea show a threefold increase in bioavailability)

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4.2 Dawn of Individualized Medication

Bgi's joint research has found that:

The medication effect of the CDP-cholinesterase gene polymorphic population (accounting for 31% of the Asian population) has increased by 47%?

Chapter Five Real-world Data of Patients

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5.1 Beneficiary Cases

A record from a tertiary hospital in Hangzhou: After combined treatment, the cerebral blood flow reserve capacity of a 62-year-old patient with cerebral infarction recovered from 32% to 89%

5.2 Self-statement of the invalid party

"Taking it for half a year continuously, the monthly expense of 300 yuan only brought about stomach discomfort" - an interview record of Ms. Li, a patient from Beijing