Composition for treating cellulite, and microneedle including same
10869905 ยท 2020-12-22
Assignee
Inventors
- Seung Yun YANG (Daegu, KR)
- Beum Soo An (Busan, KR)
- Keum Yong Seong (Busan, KR)
- Sung Min An (Yeongcheon, KR)
Cpc classification
A61K9/0019
HUMAN NECESSITIES
A61K9/0021
HUMAN NECESSITIES
A61K47/42
HUMAN NECESSITIES
International classification
Abstract
In a composition and a microneedle for a localized obesity treatment containing the same in accordance with the present disclosure, the composition in accordance with the present disclosure contains a gelatin, decomposes a fat in a body, and inhibits lipogenesis and fat deposition in the body.
Claims
1. A method for treating an individual having localized obesity, the method comprising administering a composition comprising animal-derived gelatin to the individual at a location where the individual has localized obesity, wherein the composition is administered by injection with a hypodermic needle or with a microneedle to skin tissue below the skin stratum corneum, and wherein the composition reduces adipocyte size in adipose tissue at the location where the individual has localized obesity.
2. The method of claim 1, wherein the composition is administered with the hypodermic needle.
3. The method of claim 1, wherein the individual is obese.
4. The method of claim 1, wherein the animal derived gelatin is a swine-derived gelatin.
5. The method of claim 1, wherein the animal derived gelatin is cross-linked.
6. The method of claim 5, wherein the cross-linked gelatin is cross-linked with genipin.
7. The method of claim 1, wherein the composition is administered with the microneedle.
8. The method of claim 7, wherein the microneedle comprises a tip portion having a length equal to or greater than a thickness of a skin stratum corneum of the individual.
9. The method of claim 8, wherein the microneedle is applied onto skin of the individual and at least a portion of the tip portion of the microneedle is located below the skin stratum corneum, wherein the tip portion comprises the composition, and wherein the tip portion decomposes at a position below the skin stratum corneum such that the composition is released from the tip portion and locally decomposes adipose tissue and locally inhibits lipogenesis and fat-deposition.
10. The method of claim 8, wherein the tip portion has a length of 10 m to 300 m.
11. The method of claim 10, wherein the microneedle further comprises a patch layer having a surface on which the tip portion is disposed.
12. The method of claim 11, wherein the patch layer is in contact with the skin and at least a portion of the tip portion is located below the skin stratum corneum.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE INVENTION
(10) Hereinafter, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. The present disclosure may be changed in various ways, and may be implemented in various forms. Examples of various embodiments are illustrated and described further below. It will be understood that the description herein is not intended to limit the present disclosure to the specific embodiments described. On the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the present disclosure. Examples of various embodiments are illustrated and described further below. It will be understood that the description herein is not intended to limit the claims to the specific embodiments described. On the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the present disclosure as defined by the appended claims.
(11) Hereinafter, the terminology used in the present application is for the purpose of describing particular embodiments only and is not intended to be limiting the present disclosure. As used herein, the singular forms a, an, and the are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms comprises, comprising, includes, and including, when used in the present application, specify the presence of the stated features, steps, operations, elements, components, and/or combinations thereof, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or combinations thereof.
(12) Unless otherwise defined, all terms including technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
(13) A composition for a localized obesity treatment in accordance with the present disclosure contains a gelatin, decomposes a fat in a body when injected into the body, and inhibits a lipogenesis and a fat deposition in the body.
(14) A gelatin is a kind of a derived protein obtained by treating a collagen, which is a natural protein constituting animal skin, tendon, cartilage, and the like, with hot water. The gelatin in accordance with the present disclosure may be a gelatin obtained from an animal such as a cow, a swine, and the like, or a gelatin obtained from a squid or a fish. In one example, the gelatin may be a swine-derived gelatin obtained from the swine.
(15) In this connection, the gelatin may be a cross-linked gelatin. The gelatin may be cross-linked via a cross-linked bond between amine groups that the gelatin contains. The gelatin may be cross-linked in a variety of ways. In one example, the cross-link of the gelatin may be a cross-link due to a cross-linking agent. In one example, the cross-linking agent may be a genipin. The cross-linked gelatin may be decomposed more sustainedly than the gelatin in the body, and a release speed of the gelatin in the body may be adjusted by adjusting a cross-link degree of the gelatin. In addition, a speed of the lipolysis may be adjusted based on the release speed of the gelatin.
(16) A composition containing the gelatin in accordance with the present disclosure may include a composition for a hypodermic injection for a direct in vivo injection or a composition for producing a microneedle for an in vivo injection. That is, the gelatin-containing composition may be injected directly into the living body or may be produced as the microneedle such that the gelatin may be injected into the living body by a decomposition of the microneedle. Therefore, a fat present in a periphery of an injected region of the composition may be decomposed, and the lipogenesis and the fat deposition may be suppressed.
(17) In this connection, the composition may include components such that physical properties and concentrations of the gelatin in the composition suitable for the gelatin injection into the living body or for the microneedle production may be achieved. The components may include any component that does not limit the lipolysis, lipogenesis and fat deposition inhibitory effects, and is suit for a human body. In one example, the components may include a polymer, a cross-linking agent, a plasticizer, or a solvent.
(18) The microneedle in accordance with the present disclosure contains the composition containing the gelatin in accordance with the present disclosure.
(19) The microneedle refers to a needle of a fine size. The microneedle may include a microneedle structure alone, or alternatively may further include a patch layer that has a flat face on which the microneedle structure is disposed. The patch layer may not be inserted into a skin, but is in contact with and adhered to a skin surface when the microneedle is applied onto the skin. The patch layer may exhibit elasticity and flexibility, and thus may be deformed to conform to a curved skin surface. The microneedle may be disposed on the patch layer independently, or may be a plurality of microneedles may be disposed thereon.
(20) A length of the microneedle may be equal to or greater than a thickness of a skin stratum corneum in order to be located below the skin stratum corneum when applied to the skin. The stratum corneum of the skin is an outermost layer of an epidermis that constitutes the skin. The stratum corneum protects the skin from an external environment, and prevents an evaporation of water in the body to maintain a homeostasis of the human body. The skin epidermis in which the stratum corneum is located varies in thickness from the thinnest eyelid (average 0.04 mm) to the thickest hand or sole (average 1.6 mm), and usually has a thickness of 0.05 to 0.1 mm, of which the stratum corneum has an average thickness of 0.01 mm to 0.03 mm (10 m to 30 m). Thus, a length of the microneedle in accordance with the present disclosure may be equal to or greater than 10 m, which is a length equal to or greater than a general minimum thickness of the stratum corneum. In one example, a length of the microneedle may be in a range of 10 m to 300 m, which is a range equal to or greater than a thickness of the stratum corneum, and may reach a dermis below the epidermis. Alternatively, a length of the microneedle in accordance with the present disclosure may be a few millimeters (mm) to a few centimeters (cm) in length, which is a length that may pass through the dermis to reach the panniculus adiposus. That is, a length of the microneedle in accordance with the present disclosure may range in length from a few micrometers (m) to a few millimeters (mm), or to a few centimeters (cm). The microneedle in accordance with the present disclosure has a length equal to or greater than a thickness of the skin stratum corneum. Therefore, when the microneedle is applied to the skin, a tip portion of the microneedle is located at a skin tissue below the skin stratum corneum. Then, in the skin tissue, the microneedle may be degraded (biodegraded) by an internal component such as a moisture or an enzyme to transfer the composition containing the gelatin in accordance with the present disclosure contained in the microneedle to the skin tissue. Therefore, the fat around the regions where the microneedle in accordance with the present disclosure is applied may be locally decomposed, and the lipogenesis and the fat deposition may be suppressed. More specific localized obesity treatment by the application of the microneedle in accordance with the present disclosure will be described with reference to
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(22) In a detailed description of the gelatin release of the microneedle in accordance with the present disclosure with reference to
(23) In this connection, the microneedle may release the gelatin-containing composition for three days or more. In one example, when the gelatin is the cross-linked gelatin, it may be released for a long time compared to a non-cross-linked gelatin.
(24) Hereinafter, an anti-obesity effect of the composition and the microneedle in accordance with the present disclosure will be described in detail with specific embodiments.
(25) First, in order to confirm the localized obesity treatment effect of the composition in accordance with the present disclosure, the gelatin-containing composition was produced, and an anti-obesity activity thereof was evaluated. An artificially differentiated adipocytes were extracted from an adipose tissue of a 6-week-old Sprague-Dawley male rat of a weight of about 170 g. Then, the differentiated adipocytes were treated with the gelatin-containing composition in accordance with the present disclosure (hereinafter, a gelatin composition). Then, mRNA and protein expression levels of lipogenesis and adipocyte production-related genes in the differentiated adipocytes were examined to determine the anti-obesity activity. In this connection, results of a gelatin concentration of 0.1 mg/ml (Gelatin 0.1) in the gelatin composition are shown in
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(27) A in
(28) In
(29) With reference to A in
(30) With reference to B in
(31) With reference to C in
(32) Further, with reference to D in
(33) Collectively, as described above, it may be confirmed that the FASN, which is the fat synthetase, and the SREBP-1c, and the PPARG, which are the proadipogenic transcription factor were regulated at transcription and translation levels by the gelatin-containing composition in accordance with the present disclosure, thereby reducing the protein expression. This means that the gelatin-containing composition in accordance with the present disclosure effectively exhibits the anti-obesity activity.
(34) In addition, in order to further confirm the lipolytic effect of the gelatin composition, mature adipocytes were separated from the adipose tissue of the Sprague-Dawley male rat of a weight of about 170 g. Then, 0.1 mg/ml (0.1), 1 mg/ml (1), and 2 mg/ml (2) of gelatin compositions were added to the separated adipocytes. Thereafter, the gelatin composition added adipocytes were incubated for 24 hours. The results are shown in
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(36)
(37) With reference to
(38) Thus, it may be confirmed that the gelatin composition in accordance with the present disclosure plays an important role in stimulating the lipolysis in the adipose tissue.
(39) Next, in order to confirm the anti-obesity activity of the microneedle in accordance with the present disclosure, microneedles respectively containing compositions in accordance with the present disclosure containing a non-cross-linked gelatin and a gelatin cross-linked using genipin were produced. Then the panniculus adiposus deposition inhibitory effect was confirmed using the microneedle. Microneedles produced with compositions respectively containing the non-cross-linked gelatin and 0.25% and 1.0% (percentage of the cress-linking agent (genipin) relative to the gelatin) gelatin (gelpin) as cross-linked using the genipin were attached to a skin of the rats for 2 days. Two days after the attachment of each microneedle, body weight changes of the rats and weight changes of the adipose tissues were observed. The results are shown in
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(41) A in
(42) In
(43) With reference to A in
(44) With reference to B in
(45) In order to confirm a sustained effect of the microneedle in accordance with the present disclosure, the gelpin-containing microneedles were attached to the rats for 3 days. The results are shown in
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(47) A in
(48) In
(49) With reference to
(50) That is, with reference to
(51) Further, in order to confirm an adipocyte size reducing effect of the microneedle, histological changes in the adipose tissues were observed. The adipose tissues were fixed with paraffin, and stained with H&E. Next, images of the stained adipocytes were captured with an optical microscope, and the numbers of cells were measured in diagrams. Fat deposition rates were calculated based on the numbers of the adipocytes in a restricted region. The results are shown in
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(53) A in
(54) B in
(55) With reference to A in
(56) With reference to B in
(57) Thus, it may be confirmed that the microneedle according to the present disclosure may effectively reduce the size of the adipocyte, and also reduce the fat deposition rate. That is, it may be confirmed that the microneedle according to the present disclosure may exhibit the anti-obesity characteristics.
(58) Subsequently, an influence of the microneedle on an expression of a transcriptional regulator of the adipose tissue was observed. The results are shown in
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(60) A in
(61) In
(62) With reference to A in
(63) With reference to B in
(64) With reference to C in
(65) Thus, it may be confirmed that the microneedle according to the present disclosure may control the expressions of the adipose tissue transcription factors at the transcription level. That is, it may be confirmed, by reducing the expression of the adipose tissue transcription factor of the obese rat, that the expression of the adipose tissue transcription factor may be controlled to be a level similar to that of the normal rat. This means that the microneedle in accordance with the present disclosure may treat the obesity.
(66) In order to confirm a more direct effect of the microneedle in accordance with the present disclosure, distributions and volumes of the panniculus adipose tissues were observed using a micro-CT. The results are shown in
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(68) A in
(69) B in
(70) With reference to
(71) That is, it may be confirmed that the microneedle in accordance with the present disclosure may reduce the panniculus adipose tissue at the region where the microneedle is applied, and the gelpin may be released in a sustained manner in the body based on a degree of the cross-link, thereby showing a long-term effect.
(72) In addition, an anti-obesity activity of the gelatin composition in accordance with the present disclosure, as an injectable composition. Six-week old Sprague-Dawley male rats weighing about 170 g were fed the normal and high-fat feeds for six weeks, respectively. Thereafter, in order to determine abdominal fat deposition inhibition and decomposition effects, gelatin compositions respectively containing gelatins having concentrations of 10 mg/kg, 100 mg/kg, and 150 mg/kg were respectively injected to peritoneal cavities of the rats via an intraperitoneal injection for 5 weeks. Thereafter, body weight changes of the rats and weight changes of the abdominal adipose tissue were observed. The results are shown in
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(74) A in
(75) In
(76) With reference to A in
(77) Further, with reference to B in
(78) This means, when the gelatin composition according to the present disclosure is injected as an injectable composition, that the fat is partially decomposed in the region where the gelatin composition in accordance with the present disclosure is injected while the overall body weight does not change much. Through this, it may be confirmed that the gelatin composition according to the present disclosure may be used as the injectable composition capable of exhibiting the anti-obesity activity locally.
(79) Therefore, as described above with reference to
(80) Although the present disclosure has been described in reference with a preferred embodiment, it will be understood that various modifications, and alterations may be made to the present disclosure by those skilled in the art without departing from the spirit and scope in accordance with the present disclosure as defined in the appended claims.