Compositions comprising dutasteride

Abstract

The composition of the present invention relates to a composition comprising dutasteride, wherein when administered to a human body, the composition can maintain a constant blood dutasteride concentration for a long time and continuously release its drug without precipitating dutasteride in a solid form, and also has excellent safety without causing local irritation in the administration site.

Description

Technical Field

[0001] The present invention relates to a composition comprising dutasteride as a pharmacologically active substance. Background Art

[0002] 5-α-reductase is a biocatalyst that can reduce androgen (i.e., testosterone) to dehydrotestosterone (DHT) in the prostate, trichocysts, sebaceous glands, etc. Dehydrotestosterone is known to be associated with alopecia, benign prostatic hyperplasia, etc. Therefore, 5-α-reductase inhibitors for inhibiting the production of dehydrotestosterone in tissues have been used as therapeutic agents for benign prostatic hyperplasia, and can also be used to prevent and treat alopecia.

[0003] Benign prostatic hyperplasia (BPH) (one of representative senile diseases) refers to such a disease, wherein the enlarged prostate compresses the urethra at the bottom of the bladder, thereby causing dysuria. The cause of benign prostatic hyperplasia is advanced age, the effect of androgen, etc. In the prostate, the dehydrotestosterone converted from testosterone by 5-α-reductase has an impact on the development and enlargement of the prostate, and therefore can cause benign prostatic hyperplasia. This disease can be treated by surgery to remove prostate tissue, but because most of the target patients are elderly people, there are certain limitations to suitable individuals. Therefore, due to some problems such as postoperative side effects, recurrence, etc., simple drug therapy is preferred. As this drug therapy, 5-α-reductase inhibitors can express the effect of activating anti-androgen by selectively suppressing the production of dehydrotestosterone, and reduce the increase of prostate size to alleviate dysuria.

[0004] In addition, hair loss refers to a state in which the number of hair loss caused by various reasons such as genetic factors, nutritional deficiencies, pressure is more than the average number of times. Male pattern hair loss (which is the most common type of hair loss) is known to be caused by excessive dehydrotestosterone. In particular, it is known that dehydrotestosterone causes male pattern hair loss by causing a decline in energy production and the inhibition of protein synthesis around the hair follicles, the inhibition of the proliferation of hair follicle cells, and the production of proteins that induce hair loss. In addition, it is known that tissues in hair loss areas have a higher 5-alpha-reductase activity than other scalp tissues. Therefore, 5-alpha-reductase inhibitors can effectively prevent and treat male pattern hair loss by inhibiting the production of dehydrotestosterone.

[0005] Among 5-α-reductase inhibitors, dutasteride inhibits all type I and type II 5-α-reductases and treats benign prostatic hyperplasia, male pattern hair loss, etc. by using 0.5 mg oral medication once a day. Dutasteride has no effect on testosterone that exhibits androgen effects, but only selectively inhibits the production of dehydrotestosterone, so it is considered to be a relatively safe therapeutic agent, but it is characterized by the fact that it can only work if dutasteride is taken continuously for more than several months. Moreover, benign prostatic hyperplasia or male pattern hair loss require long-term or lifelong administration of the drug. Therefore, although commercially available products only require a single dose per day, there is still a limitation that patients have low compliance with the drug.

[0006] Therefore, the present inventors have invented a composition comprising dutasteride as a pharmacologically active substance. After being administered to a human body, the composition maintains the drug concentration in the blood for a long time, and thus can improve the patient's compliance with the drug and always maintain the drug effect.

[0007] In the following, the prior art that may be relevant to the present invention is reviewed.

[0008] International Patent Publication WO 2006 / 099121 discloses a nanoparticle composition of 2000 nm or less. It describes that finasteride, dutasteride and tamsulosin can be used as applicable drugs, and also describes that phospholipids and polyoxyethylene sorbitan monooleate can be used as surface stabilizers. However, the patent is different from the present invention (i.e., a lipid-containing liquid composition) in that the composition of the patent is a composition of particles of 2000 nm or less.

[0009] International Patent Publication WO 2004 / 105694 discloses a pharmaceutical composition containing an active ingredient, vitamin E and a surfactant, and describes that the dispersibility of vitamin E can be increased by 20% according to the presence of a hydrophobic drug. However, the patent is different from the present invention in that the patent is not related to a lipid composition for injection, and also has the purpose of improving the dispersibility according to the composition when diluted in an aqueous phase.

[0010] Korean Patent Registration No. KR 10-1745425 discloses an emulsion composition of an oral composite formulation comprising dutasteride and tadalafil, and describes specific dosages of the main ingredients, oils and surfactants contained in the composition. However, the patent is different from the present invention in that the patent is not related to a lipid composition for injection and is also an emulsion composition of an oral composite formulation.

[0011] International patent publication WO 2017 / 196148 discloses a composition of a composite capsule preparation comprising dutasteride and tadalafil and a method for preparing the same, and describes a composition comprising a glycerol fatty acid ester derivative or a propylene glycol fatty acid ester derivative. However, the patent is different from the present invention in that the patent is not related to a lipid composition for injection and is also a composite capsule preparation.

[0012] Korean Patent Registration No. KR 10-1055412 discloses a solidified preparation comprising dutasteride, an adsorbent and an excipient, and describes that the solidified preparation comprises a coating solution by using a mixture of a water-soluble or water-insoluble polymer. However, the patent is different from the present invention in that the patent is not related to a lipid composition for injection and is also a solidified preparation.

[0013] Korean Patent Registration No. KR 10-1467568 discloses a composition of an external liquid preparation containing minoxidil, and describes a composition containing minoxidil with improved skin retention and hair growth effect. However, the patent is different from the present invention in that the patent is not related to an injectable lipid composition and is also a composition of an external preparation.

[0014] International patent publication WO 2010 / 015556 discloses a film-forming liquid dosage form using an active ingredient selected from finasteride or loquat (Eriobotrya Japonica) leaf extract, and the patent describes a composition of a dosage form that releases a drug for hair and scalp. However, the patent is different from the present invention in that the patent is not related to an injectable lipid composition and is also a film-forming liquid dosage form.

[0015] Prior Art References

[0016] Patent Documents

[0017] (Patent Document 1) International Publication No. WO 2006 / 099121

[0018] (Patent Document 2) International Publication Patent WO 2004 / 105694

[0019] (Patent Document 3) Korean Patent Registration Announcement No. KR 10-1745425

[0020] (Patent Document 4) International Publication Patent Publication WO 2017 / 196148

[0021] (Patent Document 5) Korean Patent Registration Announcement No. KR 10-1055412

[0022] (Patent Document 6) Korean Patent Registration Announcement No. KR 10-1467568

[0023] (Patent Document 7) International Publication Patent Publication WO 2010 / 015556 Summary of the invention

[0024] Technical issues

[0025] An object of the present invention is to provide a composition which, when administered into the body, improves patient compliance with medication by maintaining the concentration of dutasteride in the blood for a long period of time.

[0026] Technical Solution

[0027] This will be described in detail below. At the same time, each description and embodiment disclosed in the present invention can be applied to other descriptions and embodiments respectively. In other words, all combinations of the various elements disclosed in the present invention fall within the scope of the present invention. Moreover, it should not be considered that the scope of the present invention is limited to the specific description described below.

[0028] The present invention provides a composition comprising dutasteride, a lipid and an organic solvent.

[0029] The composition according to the present invention can enhance the patient's compliance with the drug and prolong the duration of the drug's action, because when the composition is applied to the human body, it does not cause precipitation of dutasteride at the application site, and has excellent sustained release, and can maintain a constant concentration of dutasteride in the blood for a long time. In addition, the composition according to the present invention has excellent safety, and does not cause local irritation symptoms such as hardening, redness, inflammation, etc. at the application site.

[0030] Particularly, in the present invention, the composition may be a composition comprising a) dutasteride, an optical isomer thereof or a pharmaceutically acceptable salt thereof; b) a lipid; and c) an organic solvent.

[0031] In the present invention, dutasteride refers to a compound represented by the following formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof:

[0032]

[0033] Described dutasteride (it is for suppressing male hormone, i.e. androgen) medicine is used for treating benign prostatic hyperplasia and male pattern hair loss.Dehydrotestosterone (converted from testosterone in the prostate) is a hormone, it causes benign prostatic hyperplasia and male pattern hair loss by increasing the size of prostate and reducing hair follicles, and testosterone is converted into dehydrotestosterone by 5-α-reductase.Dutasteride inhibits 5-α-reductase, and therefore reduces the production of dehydrotestosterone.By blocking the effect of hormone (i.e., dehydrotestosterone), dutasteride can also be used for treating benign prostatic hyperplasia, male pattern hair loss and hirsutism, or as an adjuvant for treatment after radical prostatectomy.However, the drug is characterized in that it only shows drug effect when taken for a long time for several months or longer, and its commercially available products are now oral drugs that require once a day.

[0034] Dutasteride, the pharmacologically active substance of the present invention, is a drug of the same class as finasteride, which is used for the same purpose as a 5-α-reductase inhibitor. However, compared with finasteride, which blocks only type 2 5-α-reductase, dutasteride blocks both type 1 and type 2 5-α-reductase, and thus can further reduce the production of dehydrotestosterone.

[0035] The composition of the present invention may contain dutasteride in an amount of about 1 to 50 wt %, particularly about 1 to 20 wt %, more particularly about 1 to 15 wt %, and even more particularly 2 to 12 wt %, relative to the total weight of the composition.

[0036] In the present invention, lipid refers to a hydrophobic substance that can be mixed with dutasteride, which is insoluble in water but dissolved in a non-polar solvent. The lipid is left in the application site together with dutasteride when it is applied to the human body, and then plays a role in preventing dutasteride from being precipitated into a solid in the application site. Similarly, the lipid is gradually absorbed in the body over time, and then affects the release and absorption of dutasteride. This dutasteride applied to the human body together with lipid is evenly left in the application site, and is prevented from precipitating there, so it can be continuously released into the blood. In the present invention, lipid can be selected from tocopherol, tocopherol acetate, castor oil, safflower oil, sesame oil, olive oil, almond oil, camellia oil, corn oil, cottonseed oil, soybean oil, medium chain triglycerides (MCT), pharmaceutically acceptable salts thereof and mixtures thereof, and can be particularly selected from tocopherol, tocopherol acetate, pharmaceutically acceptable salts thereof and mixtures thereof, but is not limited thereto.

[0037] The content of the lipid may be adjusted within the range that can prevent precipitation of dutasteride and show sustained release, and may be specifically about 8 to 90 wt %, more specifically about 8 to 70 wt %, even more specifically 13 to 70 wt %, relative to the total weight of the composition.

[0038] According to a specific experimental example of the present invention, it has been determined that the composition of the present invention comprising lipids does not precipitate dutasteride in the form of a solid powder, and its dissolution rate increases slowly over time to maintain a constant dutasteride concentration in the blood for a long time ( Figures 2 to 4 ).

[0039] In the present invention, the organic solvent is used as a cosolvent, added to dissolve dutasteride, making it easy to prepare a composition containing dutasteride, and providing convenience for administration by reducing the viscosity of the composition. In the present invention, the organic solvent may be selected from N-methyl-2-pyrrolidone, dimethyl sulfoxide, benzyl benzoate, benzyl alcohol, dimethylacetamide, ethanol, pharmaceutically acceptable salts thereof, and mixtures thereof, and may be particularly N-methyl-2-pyrrolidone, dimethyl sulfoxide or benzyl benzoate, but is not limited thereto.

[0040] The content of the organic solvent may be adjusted within the range of viscosity that can exhibit easy application of the composition to the human body, and may be specifically about 10 to 85 wt %, more specifically 10 to 82 wt %, even more specifically about 23 to 82 wt %, relative to the total weight of the composition.

[0041] In the present invention, the content of each component in the above composition can be adjusted within the range of viscosity that can prevent precipitation of dutasteride, show sustained release and show that the composition is easy to apply to the human body, and in particular, the composition may contain dutasteride, its optical isomer or a pharmaceutically acceptable salt thereof in an amount of about 1 to 20 wt%, a lipid in an amount of 13 to 70 wt% and an organic solvent in an amount of 10 to 82 wt%, relative to the total weight of the composition, more particularly, the composition may contain dutasteride, its optical isomer or a pharmaceutically acceptable salt thereof in an amount of 1 to 15 wt%, a lipid in an amount of 13 to 70 wt% and an organic solvent in an amount of 23 to 82 wt%, and even more particularly, the composition may contain dutasteride in an amount of 2 to 12 wt%, a lipid in an amount of 13 to 70 wt% and an organic solvent in an amount of 23 to 82 wt%.

[0042] According to a specific experimental example of the present invention, it has been determined that the composition of the present invention contains the organic solvent, so that its viscosity is reduced to facilitate its administration to the human body ( Figure 1 ).

[0043] The composition of the present invention can be simply prepared by dissolving dutasteride in lipids and the organic solvent, can be easily administered to the human body by injection, and can maintain the concentration of dutasteride in the blood for more than one week, especially more than one month, without causing precipitation of dutasteride, so the composition of the present invention shows excellent sustained release.

[0044] The composition of the present invention does not contain unsaturated fatty acid sorbitan ester, but can show excellent sustained release in the absence of unsaturated fatty acid sorbitan ester.

[0045] In addition, dutasteride (i.e., the pharmacologically active substance of the present invention) is known to be a drug that generally has good safety even when applied to the whole body for a long time. However, when applied to a local area by, for example, an ointment preparation or an injection, particularly by an injection, dutasteride causes irritation such as local edema, redness, hardening, etc. to the application site, and therefore its application is limited. Therefore, the present invention provides a composition with excellent safety, which can continuously release an active substance (i.e., dutasteride) for a long time, and also does not cause irritation symptoms such as hardening, redness, inflammation, etc. to the local area (which may occur when applied to a local area).

[0046] The composition of the present invention can be a composition for treating a disease selected from benign prostatic hyperplasia, androgenic alopecia and hirsutism. In addition, the composition of the present invention can be used as an adjuvant for treatment after radical prostatectomy.

[0047] The composition of the present invention can be administered parenterally, such as topically, and in particular by injection. The route of injection administration can be any form of administration in subcutaneous injection, intradermal injection, and intramuscular injection, and the form of administration can be appropriately selected according to the purpose of administering the composition. For example, if the composition of the present invention is used to treat benign prostatic hyperplasia, the composition can be administered around the prostate by injection. In this case, the composition can slowly release the active ingredient (i.e., dutasteride) under the skin. Similarly, if the composition of the present invention is used to treat alopecia, the composition can be administered to a specific area of ​​the head where hair growth is required by injection. In this case, the composition can slowly release the active ingredient (i.e., dutasteride) under the scalp.

[0048] The dosage of the composition of the present invention is the same as the known dosage of the pharmacologically active substance used herein, but may vary depending on the disease type, symptom degree, age, sex, etc. of the patient.

[0049] In addition, the present invention also provides a method and use for maintaining the pharmacological effect by maintaining the release of the pharmacologically active substance by administering the composition to mammals including humans.

[0050] The specific content of the composition is the same as above.

[0051] Beneficial Effects

[0052] According to the present invention, the composition comprising dutasteride, a lipid and an organic solvent is a pharmaceutical composition which can constantly maintain the blood level of the drug substance when administered to the human body and which does not precipitate the pharmacologically active substance in a solid form at the administration site, thus showing excellent safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 It is a graph showing the viscosity of Comparative Example 3 and Example 21.

[0054] Figure 2 Graphs showing the in vitro drug release behaviors of Comparative Example 1 and Example 32.

[0055] Figure 3 Graphs showing the in vivo drug release behaviors of Comparative Example 2 and Example 32.

[0056] Figure 4 It is a graph showing the in vivo drug residual amount at the administration site of Comparative Example 2 and Example 32.

[0057] Figure 5 This is an image for evaluating the in vivo safety of the composition of Example 21. DETAILED DESCRIPTION

[0058] Hereinafter, the present invention will be described in more detail by the following examples and experimental examples. However, the following examples and experimental examples are provided only for the purpose of illustrating the present invention, and therefore the scope of the present invention is not limited thereto.

[0059] The additives used in the present invention are excipients according to pharmacopoeia standards and reagents purchased from Aldrich and Croda.

[0060] [Examples 1 to 38] Preparation of the pharmaceutical composition of the present invention

[0061] Examples 1 to 38

[0062] The formulations of the present invention were prepared by using the ingredients and contents shown in Tables 1 to 3 below.

[0063] Specifically, the active ingredient (i.e., dutasteride) is mixed with an organic solvent and then dissolved at room temperature (25° C.) with a stirrer at 1000-3000 rpm for 0.5-1 hour, and then the lipid is added to the resulting solution. Thereafter, the resulting mixture is dissolved in a stirrer at about 1000-3000 rpm for about 5-30 minutes to prepare a liquid pharmaceutical composition.

[0064] Table 1

[0065]

[0066] Table 2

[0067]

[0068] Table 3

[0069]

[0070] [Comparative Examples 1 to 3]

[0071] Comparative Examples 1 to 3

[0072] In Comparative Example 1, the raw material of the active ingredient, ie, dutasteride, was used.

[0073] In Comparative Examples 2 to 3 of Table 4 below, the active ingredient (ie, dutasteride) was mixed with an organic solvent or lipid and then dissolved with a stirrer at 1000-3000 rpm for 0.5-12 hours at room temperature (25° C.) to prepare a liquid pharmaceutical composition.

[0074] Table 4

[0075]

[0076] [Experimental Example 1] Determination of the content of pharmacologically active ingredients in the composition

[0077] In order to determine the content of the pharmacologically active substance in the pharmaceutical composition prepared by the example of the present invention, the content of dutasteride (used as a pharmacologically active substance) was determined, and the results are shown in the following Table 5. The content of dutasteride was measured by HPLC, and the analysis conditions were as follows.

[0078] <HPLC Analysis Conditions of Dutasteride>

[0079] οChromatographic column: 4.6mm X 250mm, 5μm

[0080] ο Column temperature: 35°C

[0081] οDetector: UV absorption spectrophotometer (wavelength: 220nm)

[0082] oFlow rate: 1.0 mL / min.

[0083] οInjection volume: 10μl

[0084] οMobile phase: water, acetonitrile and trifluoroacetic acid (48:52:0.025)

[0085] Table 5

[0086]

[0087] As shown in Table 5, the pharmaceutical compositions of Comparative Example 2, Comparative Example 3, Example 9, Example 19, Example 21 and Example 33 showed very ideal measured values ​​within ±3% compared with the reference content (100%) of dutasteride.

[0088] [Experimental Example 2] Determination of in vitro viscosity of pharmaceutical compositions

[0089] The in vitro viscosity of the composition of the present invention was determined by the following experiment. The viscosity of Example 21 containing dutasteride, lipid and organic solvent was compared with the viscosity of Comparative Example 3 containing no organic solvent using a viscosity measuring device. The conditions for viscosity measurement were as follows.

[0090] <Measurement Conditions of Viscosity of Pharmaceutical Composition>

[0091] οViscometer: Rheometer (RHEOSENSE Inc.)

[0092] οAnalysis temperature: 25±0.5℃

[0093] The viscosity was measured and analyzed by a rheometer equipped with a thermostat, and the results are shown in Figure 1 middle. Figure 1 The results show the average of five viscosity values ​​measured.

[0094] In the case of Comparative Example 3 (excluding the organic solvent from Example 21), the five measurements of viscosity were 2553, 2565, 2557, 2547, and 2543 mPa, respectively, thus showing an average viscosity of 2553 mPa. On the other hand, in the case of Example 21 comprising dutasteride, lipid, and an organic solvent, the five measurements of viscosity were 40.5, 40.4, 40.4, 40.9, and 40.8 mPa, respectively, thus showing an average viscosity of 40.6 mPa. From the results, it can be confirmed that the composition of the present invention contains an organic solvent to reduce the viscosity of the composition, and thus can be easily administered to the human body.

[0095] [Experimental Example 3] Determination of in vitro dissolution rate of drug composition

[0096] The in vitro dissolution rate of the composition of the present invention was determined by the following experiment. Example 32 was filled into a disposable syringe in an amount equivalent to 56 mg of dutasteride and then injected into the dissolution medium, while Comparative Example 1 was directly placed in a rotating basket in an amount equivalent to 56 mg of dutasteride. The experiment was conducted according to the dissolution test method I of the Korean Pharmacopoeia 10th edition, and the dissolution conditions were as follows.

[0097] <Dissolution Conditions of Pharmaceutical Composition>

[0098] οDissolution method: Korean Pharmacopoeia Method I (Apparatus I-basket)

[0099] Dissolution medium: 900 mL of a solution containing 1% w / v sodium dodecyl sulfate

[0100] οDissolution temperature: 37±0.5℃

[0101] οSpeed: 100rpm

[0102] οTesting time: 1, 3, 6, 12 and 24 hours

[0103] Regarding the concentration of dutasteride in the dissolution sample, the dissolution rate for 24 hours was analyzed by HPLC under the conditions of Experimental Example 1, and the results are shown in Figure 2 middle.

[0104] In the case where Comparative Example 1 was directly applied to the dissolution medium containing a surfactant, only a portion of the drug was dissolved in the dissolution medium, and from 1 hour later, the dissolution rate hardly increased with the passage of time. However, in the case where Example 32 containing lipids was applied, it was confirmed that dutasteride was not precipitated in the form of a solid powder in the dissolution medium, and the dissolution rate slowly increased with the passage of time.

[0105] [Experimental Example 4] Determination of in vivo PK of a pharmaceutical composition

[0106] The drug release behavior of the composition of the present invention in vivo was determined by the following experiment. The compositions of Comparative Example 2 and Example 32 were each filled into a disposable syringe and then injected intramuscularly into the thighs of 6 9-week-old SD rats (male) weighing an average of 300 g, in an amount equivalent to 27 mg of dutasteride.

[0107] The concentration of dutasteride in SD rat plasma samples was analyzed by using LC-MS / MS (liquid chromatography / mass spectrometry) to analyze the PK (pharmacokinetic) profile, and the results are shown in Figure 3 middle.

[0108] In the case of Example 32 (i.e., a lipid composition containing dutasteride), it was determined that when administered in vivo, a constant blood concentration thereof was maintained for more than one month. On the other hand, in the case of Comparative Example 2 (i.e., a composition not containing lipids), the concentration of dutasteride in the blood was very low compared to Example 32. The reason was determined by the following Experimental Example 5 that dutasteride was precipitated in the form of powder at the application site.

[0109] From the results, it was confirmed that the composition of the present invention maintained a constant blood concentration for more than one month, thus showing excellent sustained release without precipitating dutasteride in the form of powder at the application site.

[0110] [Experimental Example 5] Determination of the amount of drug residue in the body at the administration site

[0111] The composition was administered in vivo to determine the residual amount of the drug in the administration site after a certain period of time through the following experiment. The compositions of Comparative Example 2 and Example 32 were each filled into a disposable syringe and then injected intramuscularly into the thighs of 6 9-week-old SD rats (male) weighing an average of 300 g, in an amount equivalent to 27 mg of dutasteride.

[0112] After 30 days, the rats were autopsied to collect muscle tissue from the area where the composition was applied. 20 mL of ethanol was added to the collected muscle tissue, which was then crushed with a homogenizer for about 30 minutes. Thereafter, the crushed tissue was centrifuged at 3000 rpm for 20 minutes using a centrifuge, and then the supernatant thereof was collected therefrom and quantified under the analytical conditions of dutasteride in Experimental Example 1, and the results are shown in Figure 4 middle.

[0113] For Example 32, it was determined that the residual amount of dutasteride in the administration site was about 28% within one month after administration, so 72% of the administered drug was absorbed in the body. On the other hand, for Comparative Example 2, it was determined that about 96% of dutasteride remained at the administration site even one month after administration.

[0114] From the results, it can be determined that when administered in vivo, the composition of the present invention containing lipids is continuously absorbed at the administration site, and thus a constant blood drug concentration can be maintained for a long time, but for Comparative Example 2 (i.e., a composition not containing lipids), when administered in vivo, it is determined that most of the drug stays at the administration site and is not absorbed at all. This can be explained as the reason for the in vivo PK test results in Experimental Example 3.

[0115] [Experimental Example 6] Determination of in vivo local tolerance of a drug composition

[0116] The in vivo safety of the composition of the present invention was determined by the following experiment. The composition of Example 21 was filled into a disposable syringe and then injected intramuscularly into the thighs of 6 9-week-old SD rats (male) weighing an average of 300 g, in an amount equivalent to 27 mg of dutasteride. After administration to SD rats, the presence of edema, redness, hardening, necrosis and exudate was determined from the application site by autopsy with the naked eye after 7, 14, 30 and 60 days, and the results are shown in Figure 5 middle.

[0117] like Figure 5As shown, the composition of the present invention has been determined to be a safe composition, and no irritation such as edema, redness, hardening, etc. was observed from the application site at all autopsy time points.

Claims

1. A composition comprising dutasteride or a pharmaceutically acceptable salt thereof, a lipid and an organic solvent, wherein: The lipid is selected from tocopherol, tocopherol acetate, castor oil, safflower oil, sesame oil, olive oil, almond oil, camellia oil, corn oil, cottonseed oil, soybean oil, medium chain triglycerides, pharmaceutically acceptable salts thereof, and mixtures thereof, and the amount of the lipid is 13 to 70 wt % of the total weight of the composition; The organic solvent is selected from N-methyl-2-pyrrolidone, dimethyl sulfoxide, benzyl benzoate, benzyl alcohol, dimethylacetamide, ethanol and a mixture thereof; and The composition does not contain unsaturated fatty acid sorbitan esters.

2. The composition of claim 1, wherein the lipid is selected from the group consisting of tocopherol, tocopherol acetate, castor oil, safflower oil, sesame oil, olive oil, almond oil, camellia oil, corn oil, cottonseed oil, soybean oil, medium chain triglycerides, and mixtures thereof.

3. The composition of claim 1, wherein the lipid is selected from the group consisting of tocopherol, tocopherol acetate, pharmaceutically acceptable salts thereof, and mixtures thereof.

4. The composition of claim 1, wherein the lipid is selected from the group consisting of tocopherol, tocopherol acetate, and mixtures thereof.

5. The composition of claim 1, wherein the organic solvent is selected from the group consisting of N-methyl-2-pyrrolidone, dimethyl sulfoxide, benzyl benzoate, and mixtures thereof.

6. The composition of claim 1, wherein the composition is used to treat benign prostatic hyperplasia or androgenic alopecia.

7. The composition of claim 1, wherein the composition is administered by injection.

8. The composition of claim 1, wherein the composition is administered by subcutaneous injection, intradermal injection or intramuscular injection.

9. Use of a composition comprising dutasteride or a pharmaceutically acceptable salt thereof, a lipid and an organic solvent in the preparation of a medicament for preventing or treating benign prostatic hyperplasia or androgenic alopecia, wherein: The lipid is selected from tocopherol, tocopherol acetate, castor oil, safflower oil, sesame oil, olive oil, almond oil, camellia oil, corn oil, cottonseed oil, soybean oil, medium chain triglycerides, pharmaceutically acceptable salts thereof, and mixtures thereof, and the amount of the lipid is 13 to 70 wt % of the total weight of the composition; The organic solvent is selected from N-methyl-2-pyrrolidone, dimethyl sulfoxide, benzyl benzoate, benzyl alcohol, dimethylacetamide, ethanol and a mixture thereof; and The composition does not contain unsaturated fatty acid sorbitan esters.

10. The method of claim 9, wherein the lipid is selected from the group consisting of tocopherol, tocopherol acetate, castor oil, safflower oil, sesame oil, olive oil, almond oil, camellia oil, corn oil, cottonseed oil, soybean oil, medium chain triglycerides, and mixtures thereof.

11. The method according to claim 9, wherein the organic solvent is selected from the group consisting of N-methyl-2-pyrrolidone, dimethyl sulfoxide, benzyl benzoate and mixtures thereof.

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