CN-116407497-B - Compound alfaxalone injection and preparation method thereof

Abstract

The invention belongs to the field of chemical pharmaceutical preparations for animals, and particularly discloses a compound alfasin injection. The injection takes alfaxalone and meloxicam as main active ingredients, and is added with a suspending agent and a surfactant. The injection comprises, by mass, 1-10% of alfaxalone, 0.03-0.3% of meloxicam, 0.5-5% of a suspending agent, 0.5-5% of a surfactant and the balance of water for injection. The injection is water-based nanoscale injection, has the advantages of small irritation, good stability, simple preparation process and low production cost, and is suitable for industrial mass production.

Inventors

• LI LIANG
• LV HUILIN
• HAO XIAOMEI
• Nie Fugui
• MA XIAOKANG
• FAN CHANGYOU
• LI YALING
• LIU AILING
• LI SHOUJUN
• WANG YAJIAO

Assignees

• 瑞普（天津）生物药业有限公司

Dates

Publication Date

20260512

Application Date

20211230

Claims (5)

1. 1. The compound alfasin injection is characterized by comprising the following components in percentage by mass: ; the suspending agent is a combination of glycerin and hydroxypropyl-beta-cyclodextrin, the surfactant is a combination of polyvinylpyrrolidone and lecithin, the dosage ratio of the glycerin to the hydroxypropyl-beta-cyclodextrin in the suspending agent is 1:1-3, and the carrier is water for injection.
2. 2. The compound alfaxalone injection according to claim 1, wherein the injection comprises the following components in percentage by mass: 。
3. 3. The preparation method of the compound alfasin injection according to any one of claims 1-2, comprising the following steps: (1) Crushing the raw materials of alfaxalone and meloxicam to the particle size below 50 mu m by a cyclone crusher respectively; (2) Heating a carrier with the prescription amount of 60%, adding a suspending agent with the prescription amount under stirring, dissolving until the suspending agent is clarified, preserving heat for 30 minutes, adding a surfactant with the prescription amount, stirring, dissolving, clarifying, and cooling to room temperature; (3) Adding the mixed solution prepared in the step (2) into a planetary ball mill grinding tank, and then adding the crushed prescription amount of alfaxalone and meloxicam; (4) Stainless steel grinding balls with different diameters are put into a tank body, a planetary ball mill is started after the tank is sealed, the rotation speed is set to 3000+/-50 r/min for operation, the temperature is controlled in the operation process, and the granularity D90 of a semi-finished product detection material is less than 500nm, so that the material can be discharged; (5) Discharging the ground mixture from a discharge hole, repeatedly rinsing the grinding tank and the grinding balls with a small amount of carrier, collecting rinsing liquid, mixing with the discharged material, and finally fixing the volume to the prescribed amount by using the carrier to obtain the product.
4. 4. The preparation method according to claim 3, wherein the heating temperature in the step (2) is 65-75 ℃, the ball-to-material ratio in the step (4) is 30-40:1, the control temperature is 35-45 ℃, and the running time is 8-15 hours.
5. 5. The method according to claim 4, wherein the heating temperature in the step (2) is 70 ℃, the ball-to-material ratio in the step (4) is 35:1, the control temperature is 40 ℃, and the running time is 10-13 hours.

Description

Compound alfaxalone injection and preparation method thereof Technical Field The invention belongs to the field of chemical pharmaceutical preparations for animals, and particularly relates to a compound alfasin injection and a preparation method thereof. Background In clinical practice, animals often need to be anesthetized for a variety of reasons. Anesthesia is the temporary loss of consciousness, thereby enabling the animal to operate in a resting state, and thus the animal does not feel potentially severe pain during the operation. In actual veterinary or laboratory animal studies, the anesthesia procedure or monitoring is not generally accomplished by the attending veterinarian, and is responsible for the full-time anesthesiologist. Safety is paramount, and zero tolerance is generally adopted for complications related to anesthesia, so that an anesthesiologist needs to be responsible for controlling the circulation, the respiration and the nervous system of animals, and corresponding responsibility is also required for accidental injury caused by operation or positioning and the like in the anesthesia process. More comprehensive considerations are often recommended when anesthetizing old animals, or dogs and cats with complications or systemic or genetic diseases. To perform the responsible surgery or diagnosis, long or specialized anesthesia management must be performed. Physicians are also increasingly aware of the importance of perioperative pain management, fear management or anxiety management to diseased animals. Much preparation is needed before surgery to make a complete anesthesia plan, and appropriate pre-operative evaluation of the diseased animal is needed, including but not limited to medical history, clinical symptoms, clinical examinations, laboratory examinations, and diagnoses, and the like. From the moment of seeing the pet hospital, the general sick animals have different stress reactions, such as various symptoms of body tremble, respiratory exacerbation, temporary rise of blood pressure, mania, violence, depression and the like, and certainly do not exclude some violence emotion caused by pain such as fracture, foreign body obstruction and the like. The animals need to be given a certain sedative and analgesic medicine before operation, some experienced beasts can give the preoperative sedative management to pets at home, some pet hospitals can carry out advanced analgesic management before operation, the pain threshold of the sick animals is reduced, and thus the influence of blood pressure, heart and circulation of the animals caused by pain stimulation in operation is minimized. The sedative drugs commonly used in clinic are benzodiazepines and non-benzodiazepines. Generally, sedatives other than benzodiazepines have a relatively rapid onset of action and a short duration of action, without significantly compromising the memory and attention of the animal. Before clinical operation, sedation and analgesia are often combined to ensure that the anesthesia induction in later stage can reach the anesthesia depth capable of operation stably, common sedation drugs include dexmedetomidine, etomidate and the like, and common analgesia drugs include butofil, tramadol and the like. But dexmedetomidine has the side effects of heart rhythm reduction, heart output reduction, bradycardia, hypotension and the like, and is not recommended clinically for weak and cardiovascular diseases young animals. Etomidate is highly active in myoclonus and inhibits adrenocortical hormone for 2-6 hours. The analgesic drugs are acknowledged to have the best opioid analgesic effect, but side effects and addiction become prominent problems, so that sedative drugs with small influence on cardiovascular and circulatory systems are selected, analgesic drugs with side effects and no addiction are selected, and the analgesic drugs are combined to be convenient for clinical doctors to use, and the application range is widened. The alfaxalone is a novel non-benzodiazepine steroid anesthetic, and is used for induction of general anesthesia, short surgery and surgical treatment when used by intravenous injection, and is used for sedative of pet dogs and cats when used by intramuscular injection. Meloxicam is used as non-steroidal anti-inflammatory drug, has the effects of relieving fever, easing pain and resisting inflammation, and is mainly used for easing pain and resisting inflammation clinically. The alfaxalone and meloxicam are compounded to calm and ease pain before operation for weak, heart disease, kidney disease, circulatory respiratory disease, old and young animals, which is beneficial to rapid induction into operation period. In the prior art, the preparation is basically a composite preparation of meloxicam and antibiotics, has no sedative effect, is easy to cause burst release and other problems, and has the problems of layering and precipitation after long-time placement due to the moisture contained in