LIPID PHARMACEUTICAL PREPARATION AND APPLICATION THEREOF

Abstract

A lipid pharmaceutical preparation and application thereof. The lipid pharmaceutical preparation comprises a local anesthetic and a lipid substance. The mass percentage of the local anesthetic in the lipid pharmaceutical preparation is 2%-50%. The local anesthetic is lidocaine, tetracaine, bupivacaine, articaine, cinchocaine, dibucaine, etidocaine, levobupivacaine, mepivacaine, prilocaine, ropivacaine, trimecaine, benzocaine, or procaine. The mass percentage of the lipid substances in the lipid pharmaceutical preparation is 30%-98%. The sum of the mass percentages of the components in the lipid pharmaceutical preparation is 100%. In general analgesic application, the lipid pharmaceutical preparation can produce continuous and safe analgesic effects for 12, 24, 36, 48, or 72 hours, or even longer.

Claims

1. A lipid pharmaceutical preparation, wherein, the lipid pharmaceutical preparation comprises a local anesthetic and a lipid substance, the mass percentage of the local anesthetic in the lipid pharmaceutical preparation is 2%-50%, and the local anesthetic is lidocaine, tetracaine, bupivacaine, articaine, cinchocaine, dibucaine, etidocaine, levobupivacaine, mepivacaine, prilocaine, ropivacaine, trimecaine, benzocaine, or procaine; the mass percentage of the lipid substance in the lipid pharmaceutical preparation is 30%-98%; the sum of the mass percentages of the components in the lipid pharmaceutical preparation is 100%; the lipid substance is animal fat, or, the lipid substance is animal fat and vegetable fat; the animal fat is one or more selected from the group consisting of lecithin and cholesterol.

2. The lipid pharmaceutical preparation according to claim 1, wherein, the mass percentage of the local anesthetic in the lipid pharmaceutical preparation is 3%-50%, 10%-50%, 20%-50%, 6%-50%, 6%-40%, 7%-35%, 8%-30%, 8%-24%, 10%-24% or 3%-8%; or, the local anesthetic is lidocaine, bupivacaine, ropivacaine or tetracaine; or, the mass percentage of the lipid substance in the lipid pharmaceutical preparation is 50%-98%.

3. The lipid pharmaceutical preparation according to claim 1, wherein, the melting temperature of the lipid pharmaceutical preparation is above 37° C.; or, the melting temperature of the lipid pharmaceutical preparation is 25-36° C.; or, the melting temperature of the lipid pharmaceutical preparation is 15-33° C.

4. The lipid pharmaceutical preparation according to claim 1, wherein, the lipid pharmaceutical preparation contains an anti-infection component.

5. The lipid pharmaceutical preparation according to claim 1, wherein, the lipid pharmaceutical preparation contains a water-soluble substance; or, the lipid pharmaceutical preparation contains one or more selected from the group consisting of chitin and derivative of chitin; or, the lipid pharmaceutical preparation contains hyaluronic acid or sodium hyaluronate; or, the lipid pharmaceutical preparation contains pH buffer pair.

6. The lipid pharmaceutical preparation according to claim 1, wherein, the lipid substance is animal fat and vegetable fat, the vegetable fat is soybean phospholipid, sunflower seed phospholipid or vegetable oil; or, the lipid substance is a combination of lecithin and vegetable oil or a combination of lecithin and soybean oil.

7. The lipid pharmaceutical preparation according to claim 1, wherein, the lipid pharmaceutical preparation comprises the following components by mass percentage: 3%-50% of lidocaine, 30%-90% of lecithin and 3%-20% of vegetable oil; or, the lipid pharmaceutical preparation comprises the following components by mass percentage: 5%-50% of lidocaine, 40%-85% of lecithin and 3%-20% of vegetable oil; or, the lipid pharmaceutical preparation comprises the following components by mass percentage: 15%-25% of lidocaine, 65%-85% of lecithin and 6%-15% of vegetable oil; or, the lipid pharmaceutical preparation comprises the following components by mass percentage: 3%-8% of lidocaine, 40%-70% of lecithin and 25%-55% of vegetable.

8. The lipid pharmaceutical preparation according to claim 1, wherein, the lipid pharmaceutical preparation comprises the following components by mass percentage: 5%-30% of lidocaine, 55%-85% of lecithin and 8%-15% of sodium hyaluronate.

9. A lipid pharmaceutical preparation, wherein, the lipid pharmaceutical preparation comprises lidocaine and excipients, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-50%, the excipients are excipients that can be safely absorbed by the human body, and the excipients also contain a lipid substance, the mass percentage of the lipid substance in the lipid pharmaceutical preparation is above 30%, and is not 100%; the sum of the mass percentages of the components in the lipid pharmaceutical preparation is 100%; the lipid substance is animal fat, or, the lipid substance is animal fat and vegetable fat; the animal fat is one or more selected from the group consisting of lecithin and cholesterol; after the lipid pharmaceutical preparation is embedded into human tissue, under the erosion of body fluids, the lidocaine in the lipid pharmaceutical preparation can be released in a slow-release manner from the lipid pharmaceutical preparation to the surface of the human tissue contacted by the lipid pharmaceutical preparation, and can make the patient's average blood drug concentration peak at the maximum dose not higher than 5000 ng/mL, the effective analgesic time is not shorter than 24 hours; wherein, the maximum dose is 0.5 g of the lipid pharmaceutical preparation/kg body weight.

10. The lipid pharmaceutical preparation according to claim 9, wherein, the excipients are excipients in pharmaceutical preparations that have been approved for sale by the food and drug regulating agency of China or the United States; or, the vegetable fat is soybean phospholipid, sunflower seed phospholipid or vegetable oil the lipid substance is a combination of lecithin and vegetable oil or a combination of lecithin and soybean oil.

11. The lipid pharmaceutical preparation according to claim 9, wherein, the lipid pharmaceutical preparation comprises the following components: lidocaine, lecithin and soybean oil, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-25%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 50%-85% or 50%-77%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 6%-50%, 6%-45%, 4%-25%, or 7%-25%; or, the lipid pharmaceutical preparation comprises the following components: lidocaine, lecithin and soybean oil, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-12%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 40%-75%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 20%-50%; or, the lipid pharmaceutical preparation comprises the following components: lidocaine, lecithin and soybean oil, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-15%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 40%-80%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 8%-50% or 8%-40%.

12. The lipid pharmaceutical preparation according to claim 9, wherein, the lipid pharmaceutical preparation contains an anti-infection component.

13. A lipid pharmaceutical preparation, wherein, the lipid pharmaceutical preparation comprises lidocaine and excipients, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-50%, the excipients are lipid substance that can be safely absorbed by the human body or contain a lipid substance that can be safely absorbed by the human body; the sum of the mass percentages of the components in the lipid pharmaceutical preparation is 100%; the lipid substance is animal fat, or, the lipid substance is animal fat and vegetable fat; the animal fat is one or more selected from the group consisting of lecithin and cholesterol.

14. The lipid pharmaceutical preparation according to claim 13, wherein, the lipid substance is animal fat and vegetable fat, the vegetable fat is soybean phospholipid, sunflower seed phospholipid or vegetable oil; or, the lipid substance is a combination of lecithin and vegetable oil or a combination of lecithin and soybean oil.

15. The lipid pharmaceutical preparation according to claim 13, wherein, the lipid pharmaceutical preparation comprises the following components: lidocaine, lecithin and soybean oil, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-25%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 50%-85% or 50%-77%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 6%-50%, 6%-45%, 7%-25%, or 4%-25%; the lipid pharmaceutical preparation comprises the following components: lidocaine, lecithin and soybean oil, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-12%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 40%-75%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 20%-50%; or, the lipid pharmaceutical preparation comprises the following components: lidocaine, lecithin and soybean oil, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 3%-15%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 40%-80%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 8%-50% or 8%-40%.

16. The lipid pharmaceutical preparation according to claim 13, wherein, the lipid pharmaceutical preparation contains an anti-infection component.

17. A lipid pharmaceutical preparation, wherein, the lipid pharmaceutical preparation comprises lidocaine, lecithin, vegetable oil, and chlorhexidine; the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 2%-25%, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 40%-82% or 40%-80%, the mass percentage of the vegetable oil in the lipid pharmaceutical preparation is 15%-40%, the mass percentage of the chlorhexidine in the lipid pharmaceutical preparation is 0.1%-5%; the sum of the mass percentages of the components in the lipid pharmaceutical preparation is 100%.

18. A method for treating open human body surface pain or open human tissue surface pain in a subject in need thereof, comprising: administering a lipid pharmaceutical preparation to the subject, wherein, the lipid pharmaceutical preparation is the lipid pharmaceutical preparation according to claim 1.

19. An analgesic method using a lipid pharmaceutical preparation, the lipid pharmaceutical preparation is the lipid pharmaceutical preparation according to claim 1; the analgesic method comprises the following steps: applying and maintaining the lipid pharmaceutical preparation on the open human body surface; or, maintaining the lipid pharmaceutical preparation on the surface of open human tissue surface.

20. A treatment method using the lipid pharmaceutical preparation according to claim 9, the treatment method is used to treat open human tissue surface pain.

21. The lipid pharmaceutical preparation according to claim 3, wherein, the melting temperature of the lipid pharmaceutical preparation is above 45° C.

22. The lipid pharmaceutical preparation according to claim 4, wherein, the anti-infection component is one or more of chlorhexidine, antibiotics and sulfonamides; or, the anti-infection component is chlorhexidine, the mass percentage of chlorhexidine in the lipid pharmaceutical preparation is 0.1%-5%.

23. The lipid pharmaceutical preparation according to claim 6, wherein, the lipid substance is a combination of lecithin and soybean oil, the mass percentage of the lecithin in the lipid pharmaceutical preparation is 40%-80%, and the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 8%-50%.

24. The lipid pharmaceutical preparation according to claim 11, wherein, the mass percentage of the lidocaine in the lipid pharmaceutical preparation is 15%-21%, 17%-21%, or 17%-20%, the phospholipid is lecithin, and the mass percentage of the phospholipid in the lipid pharmaceutical preparation is 62%-82% or 70%-75%, the mass percentage of the soybean oil in the lipid pharmaceutical preparation is 6%-12% or 8%-10%.

25. The lipid pharmaceutical preparation according to claim 12, wherein, the anti-infection component is one or more of chlorhexidine, antibiotics and sulfonamides; or, the anti-infection component is chlorhexidine, the mass percentage of chlorhexidine in the lipid pharmaceutical preparation is 0.1%-5%.

26. A lipid pharmaceutical preparation, wherein, the lipid pharmaceutical preparation comprises local anesthetic and excipients, the mass percentage of the local anesthetic in the lipid pharmaceutical preparation is 3%-50%, the excipients are lipid substance that can be safely absorbed by the human body or contain a lipid substance that can be safely absorbed by the human body; the sum of the mass percentages of the components in the lipid pharmaceutical preparation is 100%; the lipid substance is animal fat, or, the lipid substance is animal fat and vegetable fat; the animal fat is one or more selected from the group consisting of lecithin and cholesterol.

27. The method according to claim 18, wherein, the open human body surface pain or open human tissue surface pain is burn pain, pain during burn scab removal, incision and wound pain after anorectal surgery, or postoperative incision pain after non-anorectal surgery; or, after the lipid pharmaceutical preparation at a dose of less than or equal to 0.5 g of the lipid pharmaceutical preparation/kg body weight is applied to the open human body surface pain, the blood drug concentration peak can be less than 5000 ng/mL, or not be higher than 2500 ng/mL.

28. The analgesic method according to claim 19, the open human body surface pain or open human tissue surface pain is burn pain, pain during burn scab removal, incision and wound pain after anorectal surgery, or postoperative incision pain after non-anorectal surgery; or, when the pain to be treated is postoperative incision pain after non-anorectal surgery, the analgesic method comprises the following step: applying the lipid pharmaceutical preparation to an unstitched or partially unstitched surgical incision; or, when the pain to be treated is postoperative incision pain after non-anorectal surgery, the treatment method comprises the following step: injecting or placing the lipid pharmaceutical preparation into the surgical incision or the tissue adjacent to the surgical incision; or, when the pain to be treated is burn pain, pain during burn scab removal, or incision and wound pain after anorectal surgery, the analgesic method comprises the following step: smearing and maintaining the lipid pharmaceutical preparation on the open human body surface or open human tissue surface.

29. The lipid pharmaceutical preparation according to claim 1, wherein, the lipid substance is lipid substance in pharmaceutical preparations that have been approved for sale by the food and drug regulating agency of China or the United States; or, the effective analgesic time is not shorter than 24 hours.

30. The lipid pharmaceutical preparation according to claim 1, wherein, the mass percentage of the animal fat in the lipid pharmaceutical preparation is 50%-90%.

31. An analgesic method using a lipid pharmaceutical preparation, the lipid pharmaceutical preparation is the lipid pharmaceutical preparation according to claim 9; the analgesic method comprises the following steps: applying and maintaining the lipid pharmaceutical preparation on the open human body surface; or, maintaining the lipid pharmaceutical preparation on the surface of open human tissue surface.

32. The analgesic method according to claim 31, wherein, the open human body surface pain or open human tissue surface pain is burn pain, pain during burn scab removal, incision and wound pain after anorectal surgery, or postoperative incision pain after non-anorectal surgery; or, when the pain to be treated is postoperative incision pain after non-anorectal surgery, the analgesic method comprises the following step: applying the lipid pharmaceutical preparation to an unstitched or partially unstitched surgical incision; or, when the pain to be treated is postoperative incision pain after non-anorectal surgery, the treatment method comprises the following step: injecting or placing the lipid pharmaceutical preparation into the surgical incision or the tissue adjacent to the surgical incision; or, when the pain to be treated is burn pain, pain during burn scab removal, or incision and wound pain after anorectal surgery, the analgesic method comprises the following step: smearing and maintaining the lipid pharmaceutical preparation on the open human body surface or open human tissue surface.

33. The treatment method according to claim 20, wherein, the open human tissue surface pain is burn pain, pain during burn scab removal, incision and wound pain after anorectal surgery, or postoperative incision pain after non-anorectal surgery; or, after the lipid pharmaceutical preparation at a dose of less than or equal to 0.5 g of the lipid pharmaceutical preparation/kg body weight is applied to the open human tissue surface pain, the blood drug concentration peak can be less than 5000 ng/mL, or not higher than 2500 ng/mL; or, when the open human tissue surface pain is burn pain, pain during burn scab removal, or incision and wound pain after anorectal surgery, the method applied to the open human tissue surface pain refers to smearing the lipid pharmaceutical preparation to the open human tissue surface pain; or, when the open human tissue surface pain is postoperative incision pain after non-anorectal surgery, the method applied to the open human tissue surface pain refers to embedding the lipid pharmaceutical preparation into the postoperative incision.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0087] The present disclosure will be further explained below by means of embodiments, but the present disclosure is not limited to the scope of the described embodiments. In the following embodiments, the experimental methods without specific conditions are selected according to conventional methods and conditions, or according to the commodity specifications.

Embodiment 1

[0088] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00001 Component Mass percentage Lecithin   55% Sodium dihydrogen phosphate  0.07% Disodium hydrogen phosphate 11.93% Lidocaine   24% Glycerin    9%

[0089] The preparation method of the lipid pharmaceutical preparation is as follows:

[0090] Sodium dihydrogen phosphate, disodium hydrogen phosphate, glycerin, lidocaine, and lecithin were put into a container. The same amount of water as the weight of lecithin was added. The mixture was stirred to get a paste. The paste was baked in an oven at 80° C. for 24 hours to evaporate the water contained in it, a cream-like lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation M.

Embodiment 2

[0091] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00002 Component Mass percentage Lecithin 58% Carboxylated chitosan  4% Lidocaine 26% Glycerin 12%

[0092] The preparation method of the lipid pharmaceutical preparation is as follows:

[0093] The carboxylated chitosan was first dissolved in 10 times its weight of water. Glycerin, lidocaine and lecithin were added. The mixture was stirred to get a paste. The paste was baked in an oven at 80° C. for 24 hours to evaporate the water contained in it, a solid lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation N.

Embodiment 3

[0094] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00003 Component Mass percentage Lecithin 58% Sodium hyaluronate  4% Lidocaine 26% Glycerin 12%

[0095] The preparation method of the lipid pharmaceutical preparation is as follows:

[0096] The sodium hyaluronate was first dissolved in 20 times its weight of water. Glycerin, lidocaine and lecithin were added. The mixture was stirred to get a paste. The paste was baked in an oven at 80° C. for 24 hours to evaporate the water contained in it, a solid lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation P.

Embodiment 4

[0097] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00004 Component Mass percentage Lecithin 73% Lidocaine 18% Soybean oil  9%

[0098] The preparation method of the lipid pharmaceutical preparation is as follows:

[0099] Lidocaine, soybean oil, and lecithin were put into a container. The mixture was heated to 125° C. and stirred, and then cooled to room temperature. A cream-like lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation Q. Lipid pharmaceutical preparation Q was soft solid at 45° C.

Embodiment 5

[0100] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00005 Component Mass percentage Lecithin 59% Lidocaine 25% Soybean oil  8% Glycerin  8%

[0101] The preparation method of the lipid pharmaceutical preparation is as follows:

[0102] Lidocaine, soybean oil, lecithin and glycerin were put into a container. The mixture was heated to 125° C. and stirred, and then cooled to room temperature. A cream-like lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation R.

Embodiment 6

[0103] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00006 Component Mass percentage Lecithin   74% Sodium dihydrogen phosphate  0.07% Disodium hydrogen phosphate 11.93% Lidocaine    5% Glycerin    9%

[0104] The preparation method of the lipid pharmaceutical preparation is as follows:

[0105] Sodium dihydrogen phosphate, disodium hydrogen phosphate, glycerin, lidocaine, and lecithin were put into a container. The same amount of water as the weight of lecithin was added. The mixture was stirred to get a paste. The paste was baked in an oven at 80° C. for 24 hours to evaporate the water contained in it, a cream-like lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation S.

Embodiment 7

[0106] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00007 Component Mass percentage Lecithin 66% Lidocaine 17% Soybean oil 17%

[0107] The preparation method of the lipid pharmaceutical preparation is as follows:

[0108] Lidocaine, soybean oil, and lecithin were put into a container. The mixture was heated to 125° C. and stirred, and then cooled to room temperature. A cream-like lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation T. The melting temperature of the lipid pharmaceutical preparation T is in the range of 25-36° C.

Embodiments 8-14

[0109] The lidocaine in Embodiments 1-7 is replaced with bupivacaine.

Embodiments 15-21

[0110] The lidocaine in Embodiments 1-7 is replaced with tetracaine.

Embodiment 22

[0111] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00008 Component Mass percentage Lecithin 63.5% Lidocaine   15% Soybean oil   20% Chlorhexidine  1.5% (anti-infection component)

[0112] The preparation method of the lipid pharmaceutical preparation is as follows:

[0113] Lidocaine, soybean oil, lecithin, and chlorhexidine were put into a container. The mixture was heated to 125° C. and stirred, and then cooled to room temperature. A cream-like lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation U. The melting temperature of the lipid pharmaceutical preparation U is in the range of 25-36° C., and it has bacteriostatic effect. Compared with the lipid pharmaceutical preparation Q, the lipid pharmaceutical preparation U has a lower melting temperature and a softer texture, so it is easier to be applied to open human body surfaces, such as large burned surfaces.

Embodiment 23

[0114] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00009 Component Mass percentage Lecithin 56.5% Lidocaine   5% Soybean oil   38% Chlorhexidine   0.5% (anti-infection component)

[0115] The preparation method of the lipid pharmaceutical preparation is as follows:

[0116] Lidocaine, soybean oil, lecithin, and chlorhexidine were put into a container. The mixture was heated to 125° C. and stirred, and then cooled to room temperature. A viscous oily lipid pharmaceutical preparation was obtained, which was recorded as lipid pharmaceutical preparation V. The melting temperature of the lipid pharmaceutical preparation V is in the range of 15-33° C., and it has analgesic and bacteriostatic effects simultaneously. Compared with the lipid pharmaceutical preparation Q, and even compared with the lipid pharmaceutical preparation U, the lipid pharmaceutical preparation V has a lower melting temperature and a softer texture, so it is easier to be applied to open human body surfaces, such as large burned surfaces.

Embodiments 24-30

[0117] A lipid pharmaceutical preparation. Its components are:

TABLE-US-00010 Soybean Chlor- Carboxylated Sodium Embodiment Lidocaine Lecithin oil hexidine chitosan hyaluronate Total 24  2 wt % 90 wt % 7.9 wt %  0.1 wt % / / 100 wt % 25  3 wt % 85 wt %  9 wt % 0.2 wt % / 2.8 wt % 100 wt % 26  5 wt % 80 wt % 13 wt %   2 wt % / / 100 wt % 27  7 wt % 75 wt % 10 wt % / 4 wt %   4 wt % 100 wt % 28 15 wt % 54 wt % 30 wt %   1 wt % / / 100 wt % 29 25 wt % 55 wt % 19 wt %   1 wt % / / 100 wt % 30 30 wt % 50 wt % 20 wt % / / / 100 wt %

[0118] The preparation method of the lipid pharmaceutical preparation is as follows:

[0119] Each component is put into a container. The mixture is heated to 125° C. and stirred, and then cooled to room temperature. A viscous oily lipid pharmaceutical preparation is obtained.

[0120] The lipid pharmaceutical preparations of Embodiments 1-30 all have the following properties: in the above-mentioned lipid pharmaceutical preparations, the excipients (components other than a local anesthetic and/or chlorhexidine) are excipients that can be safely absorbed by the human body; after the above-mentioned lipid pharmaceutical preparations are embedded into human tissue or applied on open human body surface, under the erosion of body fluids, the lidocaine therein can be released from the above-mentioned lipid pharmaceutical preparation in a slow-release manner to the surface of the human tissue contacted by the above-mentioned lipid pharmaceutical preparation, and can make the patient's average blood drug concentration peak at the maximum dose not higher than 5000 ng/mL, more preferably not higher than 2500 ng/mL; the effective analgesia time is not less than 24 hours; wherein, the maximum dose is 0.5 g of the above-mentioned lipid pharmaceutical preparation/kg body weight.

Effect Embodiment 1

[0121] At the end of a patient's abdominal surgery, the fascia and muscle layer were first sutured by surgeons, and then the lipid pharmaceutical preparation M stored in a syringe was extruded and was put into the surgical incision (the length of incision was 10 cm, the extruded lipid pharmaceutical preparation M strip was also 10 cm long, so a 10 cm lipid pharmaceutical preparation M weighing 4 g was placed along the length of the incision), then the cortex was sutured.

[0122] The lidocaine in the lipid pharmaceutical preparation M, which was placed in the surgical incision, was slowly released into the incision tissue, thereby anesthetizing the incision tissue for a long time. The patient basically felt no pain for 72 hours after the surgery. Patients who had the same surgery would have severe pain for at least three days after surgery without any analgesics. The experience of this patient showed that using the lipid pharmaceutical preparation M according to the above-mentioned method of application can provide effective analgesia for at least 72 hours.

Effect Embodiment 2

[0123] At the end of a patient's abdominal surgery, the fascia and muscle layer were first sutured by surgeons, and then the lipid pharmaceutical preparation Q stored in a syringe was extruded and was put into the surgical incision (the length of incision was 10 cm, and 3 g of lipid pharmaceutical preparation Q was placed evenly along the length of the incision), then the cortex was sutured.

[0124] The lidocaine in the lipid pharmaceutical preparation Q, which was placed in the surgical incision, was slowly released into the incision tissue. The patient basically felt no pain for 72 hours after the surgery. Patients who had the same surgery would have severe pain for at least three days after surgery without any analgesics. The experience of this patient showed that using the lipid pharmaceutical preparation Q according to the above-mentioned method of application can provide effective analgesia for at least 72 hours.

Effect Embodiment 3

[0125] At the end of a patient's abdominal surgery, the fascia and muscle layer were first sutured by surgeons, and then the lipid pharmaceutical preparation S stored in a syringe was extruded and was put into the surgical incision (the length of incision was 12 cm, and 8 g of lipid pharmaceutical preparation S was placed evenly along the length of the incision), then the cortex was sutured.

[0126] The lidocaine in the lipid pharmaceutical preparation S, which was placed in the surgical incision, was slowly released into the incision tissue. The patient basically felt no pain for 72 hours after the surgery. Patients who had the same surgery would have severe pain for at least three days after surgery without any analgesics. The experience of this patient showed that the lipid pharmaceutical preparation S can provide effective analgesia for at least 72 hours.

Effect Embodiment 4

[0127] A patient's second-degree burn wound surface was very painful and was at risk of infection. The lipid pharmaceutical preparation U was smeared on the wound surface by the doctor, and then the preparation layer was covered with gauze.

[0128] Lidocaine and chlorhexidine (anti-infection component) in the lipid pharmaceutical preparation U smeared on the wound surface were slowly released into the wound surface tissue, thereby achieving the purpose of long-term analgesia. The patient basically felt no pain for 24 hours after surgery, and the risk of infection was greatly reduced.

Effect Embodiment 5

[0129] A patient's wound surface after anal fistula surgery was very painful and was at risk of infection. The lipid pharmaceutical preparation U was smeared on the wound surface by the doctor. The patient's pain, especially the pain during defecation, was greatly reduced.

[0130] Lidocaine and chlorhexidine (anti-infection component) in the lipid pharmaceutical preparation U smeared on the wound surface were slowly released into the wound surface tissue, thereby achieving the purpose of long-term analgesia and prevention of infection.

Effect Embodiment 6

[0131] A patient's second-degree burn wound surface was very painful and was at risk of infection. The lipid pharmaceutical preparation V was smeared on the wound surface by the doctor, and then the preparation layer was covered with gauze.

[0132] Lidocaine and chlorhexidine (anti-infection component) in the lipid pharmaceutical preparation V smeared on the wound surface were slowly released into the wound surface tissue, thereby achieving the purpose of long-term analgesia. The patient basically felt no pain for 24 hours after surgery, and the risk of infection was greatly reduced.

[0133] The lipid pharmaceutical preparation V has a lower viscosity than the lipid pharmaceutical preparation U, so it is easier to be smeared on the burn wound.

Effect Embodiment 7

[0134] The lipid pharmaceutical preparations N, P, Q and R, the lipid pharmaceutical preparations of Embodiments 8-21 and Embodiments 24-30, are used for surgical incisions of patients, can also provide effective analgesia for at least 72 hours.

Effect Embodiment 8

[0135] 3 g of the lipid pharmaceutical preparation Q of the present disclosure was placed into a 5 cm surgical incision (t=0 at this time) in the abdomen of a pig weighing about 10 kg that had not been sutured, and then cortical suture was performed. In this way, the lipid pharmaceutical preparation Q was sealed between the sutured fascia layer and the cortex. Wherein, the lipid pharmaceutical preparation Q contained 18 wt % of lidocaine (3 g contained 540 mg lidocaine in total), so the dose of lidocaine obtained by the pig was 54 mg/kg.

[0136] At pre-set time points over the next 72 hours, the venous blood of the pig was collected and the concentration of lidocaine in the blood sample was measured by the LC-MS method.

[0137] The above experiment with two other pigs was repeated.

[0138] The average blood drug concentrations (ng/mL) of the three pigs at these time points are listed in the table below.

[0139] In the table below, the rightmost column lists blood concentrations over time after a 60 mg/kg dose of lidocaine was administered by the method of intramuscular infusion at a constant rate for 2 hours reported by Ikeda et al. in the reference (Pharmacokinetics of Lidocaine, Bupivacaine, and Levobupivacaine in Plasma and Brain in Awake Rats; Yuko Ikeda et al.; Anesthesiology 2010; 112:1396-1403). In addition, since Ikeda et al. only reported the data of the first 4 hours, the data after 4 hours was calculated according to the industry-recognized theoretical calculation of lidocaine elimination half-life=2 hours, wherein, the English for elimination half-life is elimination half-life.

TABLE-US-00011 After the lipid pharmaceutical preparation Q of the After the preparation present disclosure was put in the reference was into the incision tissue at t = 0, infused into the muscle at a the blood drug concentration constant rate for t = 0-2 hours, of lidocaine/(ng/mL) the blood drug concentration Time/ Dose 54 mg/kg of lidocaine/(ng/mL) hour Average of the three pigs Dose 60 mg/kg 0  0 0 0.25 84 1900 0.5 133  5800 1 322  8200 2 494  10500 4 531  800 6 524  400 8 443  200 12 331  100 15 287  35.3 18 257  6.25 24 178  1.6 30 140  0.2 36 86 0 42 56 0 48 37 0 54 27 0 60 19 0 66 15 0 72 14 0

[0140] It can be seen from the data in the above table that although the doses are similar, the blood drug concentration peak of lidocaine caused by the lipid drug preparation Q is much lower than the blood drug concentration peak of lidocaine caused by the preparation used in the reference literature (industry recognized when the blood drug concentration of lidocaine greater than or equal to 5000 ng/mL would cause side effects such as increased heart rate), and the duration of the former is much longer than the latter.

[0141] Although the specific embodiments of the present disclosure are described above, those skilled in the art should understand that these are only illustrative examples, the scope of protection of the present disclosure is limited by the attached claims. Those skilled in the art can make various changes or modifications to these embodiments without deviating from the principle and essence of the present disclosure, but these changes and modifications all fall within the scope of protection of the present disclosure.