A carrier with drug sustained-release function and its application

Abstract

The present invention discloses a carrier with a drug sustained-release function and its application. The carrier is used to carry drugs and achieve a drug sustained-release effect. The carrier is in a gel state, a semi-solid state, or a solid state. The main component of the carrier is a fatty acid polyol ester, in which hydrogenated vegetable oil is dissolved. The carrier's morphology is adjusted by adjusting the amount of hydrogenated vegetable oil dissolved. The present invention mainly uses fatty acid polyol ester and hydrogenated vegetable oil to form a carrier, and then adds other drugs or compounds to achieve the purpose of sustained release. The sustained-release carrier can be prepared into an anhydrous gel, a semi-solid, or a solid, and can be used for the cavitary mucosa of animals and humans. The sustained-release carrier of the present invention does not destroy or reduce the efficacy of the active substance of the drug, and its sustained-release process is stable and effective, overcoming the shortcomings of traditional sustained-release preparations.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a carrier with a drug or compound sustained-release function and application thereof. Background Art

[0002] Periodontitis is a localized bacterial infection caused by pathogenic microorganisms within the periodontal pocket. Destruction of periodontal tissues results from the interaction between the complex subgingival microbiome and specific host defense mechanisms. Suspected periodontal pathogens are sensitive to a variety of antimicrobial agents, resulting in a wide range of treatment options, including mouthwashes, irrigations, systemic medications, and topical sustained-release and controlled-release drugs. The key to topical medication is ensuring that the drug reaches the site of lesions and maintains adequate concentration and duration. Drugs should target residual bacteria within the periodontal pocket, soft tissue pocket walls, exposed cementum, and root dentin. However, experiments have shown that many topical drugs fail to reach all of these areas. The MIC and MBC values ​​for drugs in vitro are not applicable in vivo, requiring higher drug concentrations for antimicrobial activity against bacteria in plaque biofilms. Effective drug concentrations must remain at the site of action for a sufficient time for efficacy to be achieved. Gingival crevicular fluid, the serum exudate within the gingival sulcus, has a small static volume and a high flow rate. It is estimated that the gingival crevicular fluid in a 5 mm deep periodontal pocket is replaced approximately 40 times per hour. Therefore, the local concentration of antimicrobial agents placed subgingivally will decrease rapidly, and the half-life of drugs within the gingival sulcus is approximately 1 minute. Different drugs also have different durations of action. For example, chlorhexidine kills microorganisms by disrupting their cell membranes, requiring a shorter exposure time. Antibacterial agents, such as tetracycline, inhibit bacterial protein synthesis and require a relatively longer exposure time.

[0003] Over the past 20 years, topical medications (typically sustained-release or controlled-release formulations that slowly and continuously release drugs) have become the primary method for periodontal disease treatment due to their numerous advantages, including reduced adverse reactions associated with systemic medications, high local drug concentrations, prolonged duration, and minimal or no systemic uptake. Topical medications include drug-loaded microparticles or nanoparticles, drug-loaded films, drug-loaded tubes, and injectable gels. With the exception of injectable gels, other methods are complex, time-consuming, and labor-intensive, and difficult to reach certain areas. Currently, injectable gels use polylactic acid (PLA) or poly(L-lactic acid) as the backbone carrier, and antibiotics such as tetracycline, minocycline, clindamycin, and ofloxacin as the drug carrier. PLA or poly(L-lactic acid) was originally developed for sustained-release drug implants. However, these materials have a long degradation cycle, which can take up to six months. They form a rigid solid in a liquid environment, hindering periodontal tissue regeneration and repair. Disadvantages of antibiotics include the development of resistance and the insensitivity of some bacterial strains to tetracyclines. Consequently, there is a clinical need for injectable periodontal gels that combine flexible carriers with more effective antimicrobial agents.

[0004] Currently available periodontal topical sustained-release preparations include the following: 1. Tetracycline fiber suture (Actisite) is a linear preparation made from a non-degradable vinyl acetate polymer as a sustained-release material, containing 25% tetracycline hydrochloride. After insertion into the affected area, the opening of the periodontal pocket must be sealed with cyanoacrylate adhesive to secure it within the pocket. However, its disadvantage is that the carrier material is non-biodegradable and must be removed after treatment. 2. Doxycycline gel injection (Atridox) is a biodegradable in situ gel injection, consisting of 10% doxycycline hydrochloride, 90% polylactic acid (PLA), and the solvent N-methylpyrrolidone (NMP), respectively, in two syringes. During use, two syringes are docked, pushed back and forth, and then injected into the periodontal pocket. The polymer becomes semi-solid upon contact with gingival crevicular fluid. However, its disadvantages include poor sustained-release efficacy and an initial burst release. Furthermore, the safety of N-methylpyrrolidone as a solvent remains to be verified. Furthermore, to prevent the drug from flowing back into the oral cavity from the periodontal pocket, an adhesive must be used to seal the opening of the periodontal pocket. Third, Minocycline Ointment Injection (Periocline and Dentomycin): This ointment injection contains 2% minocycline, and its carrier is composed of hydroxyethyl cellulose (HEC) and other excipients. Periocline is already available in my country under the trade name Paileo. Its disadvantages include poor sustained-release efficacy and an initial burst release. Fourth, Minocycline Microsphere Injection (Arestin): This microsphere injection contains 25% minocycline and is injected into the periodontal pocket using a periodontal syringe. However, its disadvantage is that the powdered microspheres have difficulty remaining in the periodontal affected area for long periods of time, making it difficult to maintain an effective drug concentration over time. 5. Metronidazole gel injection (Elyzol) is a white semisolid suspension containing 40% metronidazole benzoate, with monooleate and vegetable oil as carriers. The drug is injected subgingivally using a syringe. Its disadvantage is that the gel transforms into a high-viscosity liquid crystal state after encountering water in the periodontal pocket, and its residence time in the periodontal pocket is short, which is not conducive to maintaining an effective drug concentration for a long time.

[0005] The most commonly used solvents for poly(lactic-co-glycolic acid) (PLGA) or poly(lactic acid) (PLLA) are dichloromethane and N-methylpyrrolidone (NMP). The World Health Organization has determined that dichloromethane may cause cancer in humans, and the U.S. Environmental Protection Agency describes NMP as a substance of low developmental toxicity. When poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), or poly(lactic acid) (PLLA) is dissolved in N-methylpyrrolidone (NMP), upon entering the body, the solvent diffuses and spreads rapidly, quickly forming a porous structure. A large amount of water from the body fluids enters the polymer, coming into contact with the active substances within, and is released. This results in an excessively large initial spray volume and a short-lived sustained-release effect. Once the PLGA and PLA solvent NMP is released, it leaves behind a rigid solid, which is not conducive to periodontal tissue regeneration. As for other solvents, such as ethyl acetate, polyethylene glycol-400 and dimethyl sulfoxide, ethyl acetate is irritating to the eyes, nose and throat, causing bleeding gums due to vascular and nerve disorders, and can cause eczema-like dermatitis; polyethylene glycol-400 (PEG-400) is a solvent for sustained-release gel skeleton materials. After being injected into the human body, polyethylene glycol dissolves in water and diffuses too quickly. A large amount of water in the body fluid enters the polymer and comes into contact with the active substances therein and is released, resulting in an initial spray volume that is too large and a sustained-release effect that is not sustained; dimethyl sulfoxide (DMSO) is similar to NMP because it is co-soluble in water, which will result in an initial spray volume that is too large and a sustained-release effect that is not sustained. Summary of the Invention

[0006] The purpose of the present invention is to address the above-mentioned problems and provide a carrier with drug sustained-release function and its application, which is mainly used to prepare periodontal local sustained-release preparations. The present invention mainly uses fatty acid polyol esters and hydrogenated vegetable oils to form a carrier, and then adds other drugs or compounds to achieve the purpose of sustained release; the sustained-release carrier is a biodegradable flexible skeleton material that has an adhesion effect on teeth and gum tissue, overcoming the shortcomings of traditional periodontal local sustained-release preparations.

[0007] The technical solution adopted by the present invention is as follows: a carrier with a drug sustained-release function, the carrier is used to carry the drug and achieve the drug sustained-release effect, the carrier is in a gel state, a semi-solid state or a solid state, the main component of the carrier is a fatty acid polyol ester, hydrogenated vegetable oil is dissolved in the fatty acid polyol ester, and the morphology of the carrier is adjusted by adjusting the dissolved amount of hydrogenated vegetable oil.

[0008] In the present invention, the fatty acid polyol ester can be triacetin, caprylic decanoic acid glyceryl, monocaprylic glyceryl, monocaprylic glyceryl, and tricaprylic glyceryl, among which monocaprylic glyceryl, dicaprylic glyceryl, and tricaprylic glyceryl are preferred, and monocaprylic glyceryl (CAS#: 19670-49-6) is more preferred. Monocaprylic glyceryl (CMG) is an intermediate metabolite of fat and is often used as a non-toxic, highly effective, and broad-spectrum preservative. It has an inhibitory effect on Gram-like bacteria, molds, and yeasts. Like fat, it can be decomposed and metabolized in the body and eventually becomes carbon dioxide and water without any accumulation or adverse reactions. In the present invention, fatty acid polyol ester is used as a solvent for dissolving hydrogenated vegetable oil. The form of the sustained-release carrier is adjusted by adjusting the dissolving amount of the hydrogenated vegetable oil. For example, the form of the sustained-release carrier is adjusted to a gel state, and then used to prepare an injection gel. By injecting it into the periodontal affected part, since the sustained-release carrier is a flexible structure and has an adhesion effect on teeth and gingival tissue, it can reach the affected part conveniently and accurately without being easy to fall off. The medicine dissolved in the sustained-release carrier is continuously released by exudation, thereby achieving a stable sustained-release effect without sudden release. After the drug dissolution cycle ends, the remaining gel gradually degrades, and the degradation products are carbon dioxide and water. Therefore, it is not necessary to remove it after the treatment is completed, and it will not affect the regeneration and repair of periodontal tissue.

[0009] In the present invention, the hydrogenated vegetable oil can be hydrogenated coconut oil, hydrogenated palm oil, hydrogenated castor oil, hydrogenated tea seed oil, a mixture of hydrogenated castor oil and hydrogenated tea seed oil, hydrogenated linseed oil, or hydrogenated hemp seed oil, with hydrogenated castor oil being preferred. The hydrogenated vegetable oil is primarily used in the present invention to adjust the morphology of the sustained-release carrier and impart adhesion to the sustained-release carrier. Experimental studies have shown that the hydrogenated vegetable oil also improves the sustained-release effect, thereby enhancing the sustained-release effect of the sustained-release carrier to a certain extent.

[0010] In the present invention, the carrier also contains one or more of a thickener, adhesive, wetting agent, preservative, coloring agent, and flavoring agent compatible therewith. For example, the thickener can be PEG, cellulose, long-chain fatty alcohol, long-chain fatty acid and ester formed thereof, lecithin, phytosterol, etc., with an average molecular weight greater than 1000; the wetting agent can be a polyol, hyaluronic acid and its salt, plant polysaccharide, etc.; the preservative can be a guanidine cationic antimicrobial agent, a quaternary ammonium salt, an antibiotic, etc.; the coloring agent can be a food or drug pigment; and the flavoring agent can be various sweeteners and essences. These auxiliary agents are generally used as auxiliary agents, and their addition amount is less, generally about 0.01-10% (total preparation mass percentage), or directly not added.

[0011] Furthermore, in the carrier of the present invention, the mass ratio of fatty acid polyol ester to hydrogenated vegetable oil is 40-97:2-40, and the mass ratio is mainly selected according to the desired form of the carrier.

[0012] Furthermore, in the present invention, the amount of the drug added is 0.01-10.0% of the total mass of the preparation, which is determined according to the type of drug and the dosage, for example, it can be 0.01%, 0.05%, 0.1%, 0.5%, 0.8%, 0.9%, 1.0%, 1.2%, 1.6%, 1.8%, 2.0%, 2.5%, 2.8%, 4.0%, 4.2%, 4.6%, 4.8%, 5.0%, 5.5%, 6.8%, 7.5%, 8.4%, 9.6%, 10.0%, etc.

[0013] Preferably, the fatty acid polyol ester in the carrier is glyceryl monocaprylate, with a CAS number of 19670-49-6.

[0014] Preferably, the hydrogenated vegetable oil is hydrogenated castor oil.

[0015] Furthermore, the present invention also includes the use of a carrier with a drug sustained-release function in the preparation of a pharmaceutical preparation, wherein the drug is added to the above-mentioned carrier to form a pharmaceutical preparation, and the pharmaceutical preparation is applied to the cavity mucosa of animals and / or humans, such as the oral cavity, nasal cavity, vagina, rectal mucosa, etc.

[0016] Furthermore, the pharmaceutical preparation is an injectable gel preparation for treating oral diseases.

[0017] Furthermore, the injection gel preparation is mainly made of fatty acid polyol ester, hydrogenated vegetable oil and drug. Based on the total mass percentage of the injection gel preparation, the mass of fatty acid polyol ester is 40-97%, for example, it can be 40.0%, 45.0%, 57.0%, 63.5%, 75.0%, 78.0%, 80.0%, 85.2%, 88.5%, 90.0%, 92.0%, 94.0%, 97.0%, etc., and the mass of hydrogenated vegetable oil is 100%. The amount is 2-40%, for example, it can be 2.0%, 7.0%, 8.5%, 9.0%, 10.0%, 13.5%, 15.0%, 18.0%, 18.5%, 20.0%, 25.5%, 30.0%, 32.5%, 36.5%, 40.0%, etc., and the balance is the drug and other optional excipients, which are one or more compatible thickeners, adhesives, moisturizers, preservatives, colorants, and flavorings.

[0018] Furthermore, the preparation method of the injectable gel preparation of the present invention comprises the following steps:

[0019] A. Accurately weigh a designed amount of fatty acid polyol ester, take 70-90w% of the designed amount of fatty acid polyol ester, add hydrogenated vegetable oil to the fatty acid polyol ester, heat to 70-80°C to completely dissolve it, and slowly cool to 40°C while stirring to obtain mixture A;

[0020] B. Add the drug to the remaining 10-30w% of the fatty acid polyol ester, and if there are other excipients, add them together, and then homogenize and disperse them to obtain a mixture B;

[0021] C. Add mixture B to mixture A at 40°C, stir thoroughly, and slowly cool to room temperature.

[0022] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0023] 1. The sustained-release carrier of the present invention does not destroy or reduce the efficacy of the active substance of the drug. Since the sustained-release effect of the drug is achieved by drug exudation, the sustained-release process is stable and effective, avoiding the problem of sudden release.

[0024] 2. The sustained-release carrier of the present invention is a biodegradable flexible skeleton material. It not only avoids the problem of forming a rigid solid that irritates the periodontal tissue due to excessively rapid solvent release during the drug sustained-release period, but also does not need to be removed after the treatment is completed. Its degradation products are carbon dioxide and water, which are non-toxic and harmless and will not affect the regeneration and repair of periodontal tissue.

[0025] 3. The solvent used in the sustained-release carrier of the present invention is a safe, biodegradable, biocompatible, and poorly water-soluble solvent. After being compounded with hydrogenated vegetable oil, it can not only be prepared into a variety of sustained-release carriers, but also has adhesive properties. When used as a periodontal injection gel, it can adhere conveniently and accurately to teeth and gum tissue, thereby better exerting local therapeutic effects. Compared with existing injection gels, it has obvious technical advantages and great market potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a spectral scan of chlorhexidine acetate released from Group B (Formula 3) in purified water from 1 to 15 days;

[0027] Figure 2 This is the spectrum scan of Group B (Formula 3) in pure water from 13 to 27 days;

[0028] Figure 3 This is a spectral scan of chlorhexidine acetate released from Group C (Formula 2) in simulated body fluid from day 1 to day 15;

[0029] Figure 4 This is a spectral scan of chlorhexidine acetate released from group D (formulation 4) in artificial saliva from day 1 to day 15;

[0030] Figure 5 This is a spectral scan of metformin hydrochloride released from group F (formulation 6) in purified water from day 1 to day 5;

[0031] Figure 6 This is a spectral scan of metformin hydrochloride released from group G (formulation 5) in purified water from day 1 to day 5;

[0032] Figure 7 The spectral scan of the release of ranitidine hydrochloride from group H (formula 7) in purified water from 1 to 6 days;

[0033] Figure 8 This is a spectral scan of vitamin B1 released from group I (formula 8) in purified water from day 1 to day 6;

[0034] Figure 9 This is a spectral scan of benzalkonium chloride released from group J (formula 9) in pure water from 1 to 6 days. DETAILED DESCRIPTION

[0035] The present invention will be described in detail below with reference to the accompanying drawings.

[0036] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0037] Release of different drugs by sustained-release carriers

[0038] 1. Sustained-release effect of chlorhexidine acetate

[0039] 1. Experimental Materials

[0040] 1) Test samples: Formula 1, Formula 2, Formula 3, Formula 4;

[0041] 2) Drug release media: purified water (Wahaha), artificial saliva (Chuangfeng Technology), simulated body fluid (Feijing Biological).

[0042] 2. Experimental instruments

[0043] 1) UV-visible spectrophotometer (SP-756PC).

[0044] 3. Group settings

[0045] 1) Group A (0.1946 g of formula 2 sample + 30.0 g of purified water);

[0046] 2) Group B (0.2045 g of formula 3 sample + 30.11 g of purified water);

[0047] 3), Group C (0.1983 g of formula 2 sample + 30.06 g of simulated body fluid);

[0048] 4), Group D (0.2022 g of formula 4 sample + 30.06 g of artificial saliva);

[0049] 5) Group E (0.2047 g sample of formula 1 + 30.07 g artificial saliva).

[0050] 4. Experimental methods

[0051] 1) Place the experimental samples of different formulations into 2 mL syringes respectively;

[0052] 2) Squeeze about 0.2 g from a syringe without a needle, store in a 30 mL transparent bottle, and accurately weigh the experimental sample;

[0053] 3) Add approximately 30.0 g of drug release medium to each bottle;

[0054] 4) Perform the first spectral scan and measure the absorbance at 254 nm at 24 hours, and then perform a spectral scan and absorbance measurement every 48 hours;

[0055] 5) Purified water (Wahaha), artificial saliva (Chuangfeng Technology), and simulated body fluid (Feijing Biological) were used as reference solutions respectively; the test solution was taken from the solution soaked with the sustained-release carrier. After each test, the test solution was poured back into its respective transparent bottle.

[0056] 5. Experimental results

[0057] Table 1 Drug release of sustained-release carriers in water

[0058]

[0059] 1) Figure 1 This is a spectral scan of the release of chlorhexidine acetate from Group B (Formula 3) in pure water from 1 to 15 days. From the spectrum, it can be seen that it has a maximum absorption peak at 254nm, and the release trend is uniform and regularly decreasing.

[0060] 2) Figure 2 The spectrum scanning diagram of group B (formula 3) in pure water from 13 to 27 days, combined with Figure 1 It can be seen that all of them were released in about 15 days.

[0061] 3) Figure 3 This is a spectral scan of the release of chlorhexidine acetate from Group C (Formula 2) in simulated body fluid from day 1 to day 15. The spectrum shows that it has a maximum absorption peak at 254 nm, and the release trend is uniform and regularly decreasing.

[0062] 4) Figure 4 This is a spectral scan of the release of chlorhexidine acetate from Group D (Formula 4) in artificial saliva from day 1 to day 15. From the spectrum, it can be seen that it has a maximum absorption peak at 254 nm, and the release trend is uniform and regularly decreasing.

[0063] 6. Experimental Conclusion

[0064] 1) When the increase in absorbance (A) is less than 0.01, it is considered that the drug has been basically released. From the absorbance values ​​of groups A and B, it can be concluded that the sustained-release carrier can release chlorhexidine acetate evenly and regularly in pure water, and can basically maintain the release for about 15 days.

[0065] 2) From the absorbance values ​​of Group C, it can be concluded that due to the complex composition of the simulated body fluid, it is obvious that the measured absorbance is greatly affected by the reference solution. However, it can still be seen that the drug release trend of the sustained-release carrier in the simulated body fluid is uniform and regularly decreasing. From the data, it can be seen that the release can basically be maintained for about 9 days. However, since the chlorhexidine acetate content is 0.5%, the comprehensive influence of the reference solution and the comprehensive data analysis of the 5 groups in Table 1 (AE) indicate that the release period should be about 9-15 days.

[0066] 3) From the absorbance values ​​of groups D and E, it can be seen that due to the complex composition of artificial saliva, the measured absorbance is obviously greatly affected by the reference solution. However, it can still be seen that the drug release trend of the sustained-release carrier in artificial saliva is uniform and regularly decreasing. From the data, it can be seen that the release can basically be maintained for more than 15 days. However, since the chlorhexidine acetate content is 0.5%, considering the influence of the reference solution and the comprehensive data analysis of the 5 groups in Table 1 (AE), the release period should also be about 15 days.

[0067] 2. Sustained-release effect on metformin hydrochloride, ranitidine hydrochloride, vitamin B1, and benzalkonium chloride

[0068] 1. Experimental Materials

[0069] 1) Test samples: Formula 5, Formula 6, Formula 7, Formula 8, Formula 9;

[0070] 2) Drug release medium: purified water (Wahaha).

[0071] 2. Experimental instruments

[0072] 1) UV-visible spectrophotometer (SP-756PC).

[0073] 3. Group settings

[0074] 1) Group F (0.1990 g of formula 6 sample + 30.11 g of purified water);

[0075] 2) Group G (0.2016g of formula 5 sample + 30.14g of purified water)

[0076] 3) Group H (0.2087 g of formula 7 sample + 30.11 g of purified water);

[0077] 4) Group I (0.2016 g of formula 8 sample + 30.12 g of purified water);

[0078] 5) Group J (0.0975 g of formula 9 sample + 30.18 g of purified water).

[0079] 4. Experimental methods

[0080] 1) Place the experimental samples of different formulations into 2 mL syringes respectively;

[0081] 2) Squeeze about 0.2 g (about 0.1 g for carrier containing benzalkonium chloride) from a syringe without a needle, store in a 30 mL transparent bottle, and accurately weigh the experimental sample;

[0082] 3) Add about 30.0g of purified water to each bottle;

[0083] 4) Perform spectral scanning every 24 hours and measure absorbance at 232 nm (metformin hydrochloride), 313 nm (ranitidine hydrochloride), 261 nm (vitamin B1), and 219 nm (benzalkonium chloride);

[0084] 5) Groups H, I, and J used purified water (Wahaha) as the reference solution; Groups F and G used Formulation 2 (blank) and Formulation 3 (blank) without metformin hydrochloride as blank carriers. Reference solutions were prepared according to steps 1-3 in "4. Test Methods". The test solutions and the reference solutions of Groups F and G were taken from the solutions soaked with the sustained-release carrier. After each test, the test solutions were poured back into their respective transparent bottles.

[0085] 4. Experimental results

[0086] Table 2 Release of sustained-release carriers containing different drugs in water

[0087]

[0088] 1) Figure 5 This is a spectral scan of the release of metformin hydrochloride from group F (formulation 6) in pure water from 1 to 5 days. From the spectrum, it can be seen that it has a maximum absorption peak at 232nm, and the release trend is uniform and regularly decreasing.

[0089] 2) Figure 6This is a spectral scan of the release of metformin hydrochloride from group G (formula 5) in pure water from 1 to 5 days. It can be seen from the spectrum that it has a maximum absorption peak at 232nm, and the release trend is uniform and regularly decreasing.

[0090] 3) Figure 7 This is a spectral scan of the release of ranitidine hydrochloride from group H (formula 7) in pure water from day 1 to day 6. From the spectrum, it can be seen that it has a maximum absorption peak at 313 nm, and the release trend is uniform and regularly decreasing.

[0091] 4) Figure 8 This is a spectral scan of vitamin B1 released from group I (formula 8) in pure water from 1 to 6 days. It can be seen from the spectrum that there is a maximum absorption peak at 261nm, and the release trend is uniform and regularly decreasing.

[0092] 5) Figure 9 This is a spectral scan of the release of benzalkonium chloride from Group J (Formula 9) in pure water from 1 to 6 days. From the spectrum, it can be seen that it has a maximum absorption peak at 219 nm, and the release trend is uniform and regularly decreasing.

[0093] 5. Experimental Conclusion

[0094] When the increase in absorbance (A) is less than 0.01, it is considered that the drug has been basically released. From the absorbance values ​​of groups F and J, it can be concluded that the sustained-release carrier slowly releases metformin hydrochloride in pure water and maintains the release for 3 days; it slowly releases ranitidine hydrochloride, vitamin B1, and benzalkonium chloride and maintains the release for 4 days. 3. Specific embodiments

[0096] Example 1

[0097] The following raw materials are used to prepare the product according to mass percentage: 40.0-97.0% of monocaprylin, 2.0-40.0% of hydrogenated castor oil, and 0.01-10.0% of chlorhexidine acetate.

[0098] Preparation method:

[0099] A. Accurately weigh the designed amount of fatty acid polyol ester, take 80w% of the designed amount of monocaprylin, add hydrogenated castor oil to the monocaprylin, heat to 70-80°C to completely dissolve it, and slowly cool to 40°C while stirring to obtain mixture A;

[0100] B. adding chlorhexidine acetate to the remaining 20 w% of monocaprylin, and then homogenizing and dispersing the mixture to obtain a mixture B;

[0101] C. Add mixture B to mixture A at 40°C, stir thoroughly, and slowly cool to room temperature.

[0102] Example 2

[0103] Table 3 lists the raw materials and their mass ratios of 14 formulations. For each formulation, the raw materials were taken according to the mass ratio and homogeneous preparations were prepared according to the preparation method of Example 1.

[0104] Table 3 Recipe raw materials and their mass percentage (%)

[0105] project HCO GC CHX MH RH VB1 BZK Recipe 1 4.0 95.50 0.5 — — — — Recipe 2 6.0 93.50 0.5 — — — — Recipe 3 8.0 91.50 0.5 — — — — Recipe 4 10.0 89.50 0.5 — — — — Recipe 5 6.0 93.93 — 0.07 — — — Recipe 6 8.0 91.85 — 0.15 — — — Recipe 7 6.0 93.75 — — 0.25 — — Recipe 8 8.0 91.50 — — — 0.5 — Recipe 9 12.0 87.30 — — — — 0.7 Recipe 10 18.0 71.00 1.0 — — — — Recipe 11 25.0 74.00 — 1.0 — — — Recipe 12 30.0 68.50 — — 1.5 — — Recipe 13 35.0 63.00 — — — 2.0 — Recipe 14 40.0 59.00 — — — — 1.0

[0106] Note: HCO is hydrogenated castor oil; GC is glyceryl monocaprylate; CHX is chlorhexidine acetate; MH is metformin hydrochloride; RH is ranitidine hydrochloride; VB1 is vitamin B1; BZK is benzalkonium chloride.

[0107] Example 3

[0108] Table 4 lists the raw materials and their mass ratios of 8 formulations containing other auxiliary materials. For each formulation, the raw materials were taken according to the mass ratio and a homogeneous paste was prepared according to the preparation method of Example 1.

[0109] Table 4 Formula raw materials containing other excipients and their mass percentage (%)

[0110] project HCO GC CHX MH thickener moisturizer Colorants Recipe 15 4.0 93.50 0.5 — 2.0 — — Recipe 16 4.0 94.50 0.5 — — 1.0 — Recipe 17 4.0 95.49 0.5 — — — 0.01 Recipe 18 4.0 94.49 0.5 — — 1.0 0.01 Recipe 19 8.0 90.85 — 0.15 1.0 — — Recipe 20 8.0 90.85 — 0.15 — 1.0 — Recipe 21 8.0 91.84 — 0.15 — — 0.01 Recipe 22 8.0 91.34 — 0.15 — 0.5 0.01

[0111] Note: HCO is hydrogenated castor oil; GC is glyceryl monocaprylate; CHX is chlorhexidine acetate; MH is metformin hydrochloride; thickener is PEG-1000; moisturizer is glycerol; colorant is food grade blue pigment.

[0112] Comparative Example 1

[0113] The formula of Comparative Example 1 is: 8.0% hydrogenated castor oil, 0.5% chlorhexidine acetate, and 91.50% N-methylpyrrolidone. Its preparation method is the same as that of Example 1.

[0114] Comparative Example 2

[0115] The formula of Comparative Example 2 is: 8.0% hydrogenated castor oil, 0.5% chlorhexidine acetate, and 91.50% ethyl acetate. Its preparation method is the same as that of Example 1, except that it is only heated to 50°C.

[0116] Comparative Example 3

[0117] The formula of Comparative Example 3 is: 8.0% hydrogenated castor oil, 0.5% chlorhexidine acetate, and 91.50% dimethyl sulfoxide. Its preparation method is the same as that of Example 1.

[0118] Comparative Example Experimental Results

[0119] Comparative Example 1: After heating, hydrogenated castor oil can be dissolved in N-methylpyrrolidone, but cannot form a homogeneous gel after cooling to room temperature.

[0120] Comparative Example 2: When heated to about 50°C, hydrogenated castor oil cannot be dissolved in ethyl acetate.

[0121] Comparative Example 3: After heating, hydrogenated castor oil is insoluble in dimethyl sulfoxide.

[0122] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. Use of a carrier with drug sustained-release function in the preparation of a pharmaceutical preparation, characterized in that: The carrier is used to carry drugs and achieve a sustained-release effect. The carrier is in a gel, semi-solid, or solid state. The main component of the carrier is monocaprylin, in which hydrogenated castor oil is dissolved. The carrier's morphology is adjusted by adjusting the amount of hydrogenated castor oil dissolved. The mass ratio of monocaprylin to hydrogenated castor oil is 40-97:2-40. The carried drug or compound is chlorhexidine acetate. The carrier can sustain the release of chlorhexidine acetate for 15 days in pure water.

2. The use according to claim 1, characterized in that The carrier may also contain one or more of a thickener, an adhesive, a moisturizer, a preservative, a colorant, and a flavoring agent that are compatible with the carrier.

3. The use according to claim 1, characterized in that The amount of the drug added is 0.01-10.0% of the total mass of the preparation.

4. The use according to any one of claims 1 to 3, characterized in that The drug is added to a carrier to form a drug preparation, which is applied to the cavitary mucosa of animals and / or humans.

5. The use according to claim 4, characterized in that The pharmaceutical preparation is an injection gel preparation for treating oral diseases.

6. The use according to claim 5, characterized in that The preparation method of the injection gel preparation comprises the following steps: A. Accurately weigh a designed amount of monocaprylin, taking 70-90w% of the designed amount of monocaprylin, adding hydrogenated castor oil to the monocaprylin, heating to 70-80°C to completely dissolve it, and slowly cooling to 40°C while stirring to obtain a mixture A; B. Add the drug to the remaining 10-30w% of monocaprylin, and if there are other excipients, add them together, and then homogenize and disperse them to obtain mixture B; C. Add mixture B to mixture A at 40°C, stir thoroughly, and slowly cool to room temperature.

Images