Orlistat powder is white crystalline powder and solid at room temperature. The molecule is a stereoisomer with two chiral centers, so there are four stereoisomers, of which only ( S ) -Orlistat has obvious biological activity. The molecule is composed of two long-chain fatty acyl side chains and an α, β-unsaturated acid at the end. It has high affinity with the target enzyme lipase and can occupy its active center, thereby preventing the hydrolysis of triglyceride by lipase and inhibiting fat absorption in the digestive system. It is almost insoluble in water, but can be dissolved in polar organic solvents ( such as ethanol, chloroform, dimethyl sulfoxide, etc. ), and its maximum solubility is about 0.5 mg / mL. It is a drug used to treat obesity, which mainly reduces the absorption and metabolism of fat in the body by inhibiting lipase.
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| Chemical Formula | C29H53NO5 |
| Exact Mass | 495.39 |
| Molecular Weight | 495.75 |
| m/z | 495.39 (100.0%), 496.40 (31.4%), 497.40 (2.7%), 497.40 (2.0%), 497.40 (1.0%) |
| Elemental Analysis | C, 70.26; H, 10.78; N, 2.83; O, 16.14 |
Orlistat powder is the world's first approved oral anti obesity drug with non central nervous system effects, and currently the only oral weight loss drug approved as an over-the-counter (OTC) in China. It has a wide range of uses and clear scientific basis.
The core purpose is weight management, especially suitable for overweight or obese adults who require additional assistance on the basis of diet and exercise. It inhibits the activity of lipase in the gastrointestinal tract, preventing the breakdown and absorption of fat in food, making undigested fat unable to be absorbed by the intestine and excreted with feces. This mechanism of action reduces calorie intake and helps control weight.
Mechanism of action: By forming covalent bonds with the active serine sites of gastric lipase and pancreatic lipase in the stomach and small intestine lumen, the enzymes are inactivated. Inactivated enzymes cannot hydrolyze fats (mainly triglycerides) in food into absorbable free fatty acids and monoacylglycerols, thereby reducing calorie intake.
Weight loss effect: Clinical data shows that combined with lifestyle interventions, an average weight loss of about 6 kilograms (equivalent to 7.5% of baseline weight) can be achieved after 24 weeks of treatment. This effect can be sustained over long-term use, helping obese or overweight patients achieve their healthy weight goals.
Applicable population: It is applicable to adults with body mass index (BMI) over 24, including simple obesity patients and overweight people with obesity related diseases such as hypertension and diabetes. For obese patients with a BMI exceeding 28, it can be used as an important weight management tool.
The applicable population is not limited to general obese or overweight patients, but also extends to weight management needs under specific health conditions.
The subdivision of overweight and obesity: Overweight usually refers to a BMI between 24 and 28, while obesity refers to a BMI above 28. Orlistat is suitable for both populations, but it should be noted that it is not recommended for people with a BMI below 24.
Obese patients with metabolic abnormalities: For obese people with metabolic syndrome (such as type 2 diabetes and hyperlipidemia), orlistat not only contributes to weight loss, but also improves related metabolic indicators, such as lowering cholesterol and blood sugar levels.
Obese patients at specific stages of life: Although pregnant, lactating women, and adolescents under 18 years old should not use orlistat, weight loss can help improve fertility for obese women of childbearing age. For example, research has shown that orlistat has weight loss and ovulation induction effects on overweight and obese infertile women.
While losing weight, it can also improve obesity related metabolic abnormalities and provide comprehensive health management for obese patients.
Lowering blood lipid levels: Orestat reduces total cholesterol and low-density lipoprotein cholesterol by inhibiting the absorption of triglycerides in the intestine, thereby assisting in lowering blood lipid levels. This is particularly important for patients with hyperlipidemia, as it helps reduce the risk of cardiovascular disease.
Improve blood sugar control: For type 2 diabetes patients with obesity, orlistat can help manage symptoms by increasing insulin sensitivity and improving blood sugar control. Before starting treatment, fasting blood glucose and glycated hemoglobin should be checked and regularly monitored to ensure effective control of blood glucose levels.
Auxiliary hypotensive effect: It can dilate peripheral blood vessels, reduce cardiac afterload, and thus play an auxiliary hypotensive role. This is usually used as an adjuvant therapy for patients with mild or moderate primary hypertension, but attention should be paid to avoiding blood pressure elevation caused by vigorous exercise and taking according to the prescribed dosage.
In addition to weight management and improvement of metabolic abnormalities, it also plays a role in interventions for certain specific health issues.
Polycystic ovary syndrome (PCOS) related obesity: PCOS patients often have obesity and insulin resistance. Losing weight and improving insulin sensitivity can help alleviate PCOS symptoms and increase fertility.
Prevention of weight rebound after weight loss surgery: For patients who have undergone weight loss surgery but experience weight rebound, it can be used as an adjuvant treatment to help maintain the surgical effect and prevent weight from rising again.
Weight management for specific occupations or lifestyles: For individuals who are obese or overweight due to occupations (such as athletes, models) or lifestyles (such as prolonged sitting, high calorie diets) that require maintaining a specific weight range, orlistat powder can provide effective weight management support.
synthesis Method
the synthesis of 3-chloropropyl trimethoxysilane
3-Chloropropanyltrimethoxysilane is the starting material for Orlistat, which can be synthesized by the following steps:
1
Dissolve 3-chloropropane in ethanol, add trimethoxysilane, and stir at 0°C for 30 min.
2
Add aluminum trichloride and continue to stir for 1 h. After the reaction is complete, dilute the reaction solution with water and extract.
3
Neutralize the organic phase with concentrated aqueous NaOH and wash with saturated aqueous NaCl.
4
Dry and concentrate to obtain 3-chloropropanetrimethoxysilane with a yield of 84%.
the synthesis of trimethoxysilyl acrylate
3-Chloropropyltrimethoxysilane reacts with thiourea in ethanol to generate 3-thioureidotrimethoxysilane, which is then hydrolyzed to obtain trimethoxysilyl acrylate:
1
Dissolve thiourea in ethanol, add 3-chloropropanyltrimethoxysilane, and heat the reaction at 50°C for 2 h.
2
Neutralize the organic phase with concentrated aqueous NaOH and wash with saturated aqueous NaCl.
3
Dry and concentrate to obtain 3-thioureidoacrylic trimethoxysilane with a yield of 78%.
4
Exchange methoxyl groups of 3-thioureidotrimethoxysilane acrylate and NaOH in ethanol to obtain trimethoxysilyl acrylate with a yield of 91%.
Synthesis of Orlistat
The esterification reaction of trimethoxysilyl acrylate and hexanoic acid under the catalysis of sodium lauryl sulfate produces the precursor compound hexyl-3,5-dimethylhexanoate of Orlistat:
1
Put trimethoxysilyl acrylate in dry xylene, add hexanoic acid and sodium lauryl sulfate, and react at 120°C for 20 h.
2
Dilute the reaction solution with water and extract the organic phase.
3
Neutralize the organic phase with concentrated aqueous NaOH and wash with saturated aqueous NaCl.
4
Dry and concentrate to obtain hexyl-3,5-dimethylhexanoate with a yield of 67%.
Finally, this precursor compound is hydrolyzed under the catalysis of acetic acid to obtain Orlistat:
React hexyl-3,5-dimethylhexanoate with NaOH in ethanol to produce Orlistat with a yield of 92%.
The chemical structure employed by Orlistat powder is based on epoxy compounds. In the molecule of Orlistat, it mainly consists of three parts: 1) an epoxy structure; 2) a polarizing structure; 3) a fatty acyl chain.
1. Epoxy structure:
Orlistat's molecule contains an epoxy structure, which is a key component of its ability to inhibit pancreatic lipase. Epoxy compounds refer to organic compounds containing a three-membered heterocyclic ring (oxygen atom and two carbon atoms). In Orlistat's molecule, the epoxy structure is composed of two oxygen atoms and two adjacent carbon atoms, one of which is responsible for binding to pancreatic lipase, and the other is connected to the polarizing structure. The presence of the epoxy structure increases the activity of Orlistat and improves its efficacy.
2. Polarization structure:
Orlistat's molecule also contains a polarizing structure consisting of a nitrogen atom and a carboxyl group. The polarized structure can increase the affinity between Orlistat and pancreatic lipase, and make it easier to enter the intestinal tract and absorb it. At the same time, it can also improve the efficacy of Orlistat by acting as a proton acceptor. The existence of the polarizing structure enables Orlistat to act faster and more effectively in the body, so as to achieve the purpose of reducing the weight of obese patients and improving the metabolic status.
3. Fatty acyl chains:
Orlistat's molecule also contains a fatty acyl chain, which is a chain-like structure containing atoms such as carbon, hydrogen and oxygen. This chain is an important component of Orlistat because it is essential for Orlistat's ability to inhibit pancreatic lipase activity. Fatty acyl chains can bind to the catalytic triad of pancreatic lipase to form an irreversible complex that prevents pancreatic lipase from hydrolyzing triacylglycerols to free fatty acids and glycerol. Therefore, the fatty acyl chain of Orlistat is one of the important factors that can reduce intestinal absorption of fat and reduce body weight.
What are the side effects of this compound?
The most common side effect of orlistat is discomfort symptoms related to the digestive system. These symptoms are usually caused by drugs blocking the absorption of fat, resulting in unabsorbed fat being excreted with feces, leading to a series of digestive problems：
Gastrointestinal bloating: Due to incomplete absorption of fat in the intestine, a large amount of gas is produced, leading to gastrointestinal bloating. Patients may feel bloating, abdominal pain, or discomfort.
Fecal urgency: Some patients may feel a sudden strong urge to defecate after taking orlistat. This may be due to intestinal irritation caused by medication.
Increased frequency of bowel movements: After taking Orlistat, patients may notice a significant increase in frequency of bowel movements. This is because the medication promotes the faster passage of unabsorbed fat through the intestine, leading to an increase in bowel movements.
Fecal incontinence: In rare cases, patients taking Orlistat may experience symptoms of fecal incontinence. This is usually caused by medication induced intestinal dysfunction.
Fatty diarrhea: Fatty diarrhea is a common side effect of Orlista, which is manifested by a large amount of fat in the stool, in the form of foam or water. This symptom may cause patients to frequently use the restroom, affecting their daily life.
Another common side effect is oily spots and oily secretions. This is because the drug blocks the absorption of fat, causing it to be excreted through the skin.
Oil spots: Oil spots usually appear on the patient's clothing, bed sheets, or skin. These spots may appear yellow or orange and have a greasy feel.
Oily discharge: In addition to oily spots, patients may also notice oily discharge in certain parts of the body, such as the armpits and groin. These secretions may have an odor and affect the patient's personal hygiene.
3.Potential serious side effects
Hepatotoxicity: Long term or excessive use of orlistat may cause damage to the liver, leading to abnormal liver function. Patients may experience symptoms such as jaundice and liver pain. If these symptoms occur, stop taking medication immediately and seek medical attention.
Vitamin deficiency: Orlistat blocks the absorption of fat and may also affect the absorption of fat soluble vitamins such as vitamins A, D, E, and K. Long term use of Orlistat may result in symptoms of vitamin deficiency, such as dry skin, decreased vision, osteoporosis, etc. Therefore, patients should regularly supplement vitamins during the use of orlistat.
Gallstones: Patients taking Orlistat may increase their risk of developing gallstones. This is because the medication blocks the absorption of fat, leading to an increase in cholesterol levels in bile and thus increasing the formation of gallstones.
Cardiac arrhythmia: In rare cases, patients taking Orlistat may experience symptoms of cardiac arrhythmia. This may be due to the stimulation of the cardiac nervous system by the medication. If arrhythmia occurs, seek medical attention immediately.
Pancreatitis: Although orlistat usually does not cause pancreatitis, in some cases, such as when the patient is at risk of pancreatitis (such as alcohol abuse, biliary tract disease, etc.), taking orlistat may increase the risk of pancreatitis.
4.Drug interactions
Orlistat powder may interact with other drugs, affecting their efficacy or increasing the risk of side effects. Here are some common drugs that interact with orlistat:
Anticoagulants, such as warfarin, may increase the risk of bleeding when used in combination with orlistat. Therefore, when using these medications, patients should consult a doctor and adjust the dosage.
Antiepileptic drugs: When used together with orlistat, antiepileptic drugs such as carbamazepine may reduce their efficacy. Therefore, when using these medications, patients should consult a doctor and consider switching to other antiepileptic drugs.
Immunosuppressants: When immunosuppressants such as cyclosporine are used together with orlistat, the toxicity of immunosuppressants may increase. Therefore, when using these medications, patients should consult a doctor and adjust the dosage.
Other weight loss medications: When used in combination with other weight loss medications such as fenfluramine, there may be an increased risk of side effects. Therefore, when using these medications, patients should consult a doctor and avoid using them simultaneously.
faq
Is orlistat effective for weight loss?
Orlistat effectively lowers body weight, BMI, cholesterol levels, and waist circumference. It has also been shown to cause a modest decrease in blood pressure and improved glycemic control in patients with diabetes. Gastrointestinal adverse effects are the most common reason for discontinuation of the medication.
Is Ozempic the same as orlistat?
You can buy orlistat (brand name: Xenical/Alli) as an over-the-counter alternative to Ozempic in the UK. However, orlistat is a very different type of weight-loss medication and is less effective than Ozempic at supporting weight loss.
How much weight can you lose with orlistat in a month?
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